Rheumatoid Arthritis: Sweden

Forsgren S, Grimsholm O, Jönsson M, Alfredson H, Danielson P. · Department of Integrative Medical Biology, Section for Anatomy, Umeå University, SE-901 87 Umeå, Sweden. · Life Sci. · Pubmed #19409915 No free full text.

Abstract: For certain parts of the body, it is nowadays accepted that there is a cholinergic system that is not related to cholinergic innervation, i.e. a non-neuronal cholinergic system. It might be argued that this system is of minor importance. New information obtained shows, however, that the non-neuronal cholinergic system is more widely distributed in the body than what is previously recognised. In recent studies, the existence of such a system has thus been shown for human tendons, especially in chronically painful situations (tendinopathy/tendinosis), in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis, and in the mucosa of ulcerative colitis patients. There is evidence of both acetylcholine (ACh) production and a marked existence of muscarinic (M2) ACh receptors in these situations. The non-neuronal cholinergic system may be involved in the establishment of a 'cholinergic anti-inflammatory pathway' and in proliferative and tissue reorganisation processes via autocrine/paracrine effects. The new information obtained suggests that this system plays an important functional role in chronically painful tendons and in inflammatory conditions. The findings of such a system in various parts of the body, when taken together, show that not only should the classical neuronal cholinergic system be considered in discussion of the cholinergic influences in the body. Additionally, the production of ACh in local cells in the tissues represents an important extra supply of the transmitter. ACh effects can be obtained whether or not there is a cholinergic innervation in the tissue.

Rantapää-Dahlqvist S. · Department of Rheumatology, University Hospital, Umeå SE-901 85, Sweden. · Curr Opin Rheumatol. · Pubmed #19365265 No free full text.

Abstract: PURPOSE OF REVIEW: To give an overview of publications on presence of autoantibodies, rheumatoid factor and anticitrullinated protein/peptide antibodies (ACPAs) and their relationships to genetic markers and soluble factors as indicators of immune activation and identified predating the onset of symptoms of rheumatoid arthritis (RA). RECENT FINDINGS: The development during recent years concerning autoantibodies with high specificity for RA, ACPAs, has confirmed previous findings of presence of autoantibodies, such as rheumatoid factors and antikeratin antibodies, years before disease onset. Particularly, ACPAs in combination with human leukocyte antigen-shared epitope alleles and PTPN22 1858T carriage increased the relative risks of developing RA compared with not having these factors. Both shared epitope alleles and 1858T variant seemed to contribute to development of ACPAs rather than independently contribute to RA. Soluble factors such as hypersensitive C-reactive protein, cytokines, cytokine receptors and chemokines are upregulated before disease onset, though, not as long antedating time as ACPAs and rheumatoid factors. SUMMARY: Presence of ACPAs and rheumatoid factors are present several years before disease onset suggesting a gradual process leading to the development of RA. Genetic markers such as shared epitope alleles and PTPN22 1858T variant increase the relative risk for disease development. Soluble immunological markers are also increased closer to the onset of symptoms indicating activation of the immune system.

Ivanov S, Lindén A. · AstraZeneca R&D Lund, S-221 87 Lund, Sweden. · Trends Pharmacol Sci. · Pubmed #19162337 No free full text.

Abstract: Interleukin (IL)-17 (now synonymous with IL-17A) is an archetype molecule for an entire family of IL-17 cytokines. Currently believed to be produced mainly by a specific subset of CD4 cells, named Th-17 cells, IL-17 is functionally located at the interface of innate and acquired immunity. Specifically, it induces the release of chemokines and growth factors from mesenchymal cells and is now emerging as an important local orchestrator of neutrophil accumulation in several mammalian organs. Furthermore, there is growing evidence that targeting IL-17 signaling might prove useful in a variety of diseases including asthma, Crohn's disease, multiple sclerosis, psoriatric disease and rheumatoid arthritis. Here, we summarize the key aspects of the biology of IL-17 in mammals and scrutinize the potential pharmacological use of targeting IL-17 in humans.

Turesson C, Matteson EL. · Department of Rheumatology, Malmo University Hospital, Malmo, Sweden. · Curr Opin Rheumatol. · Pubmed #19077716 No free full text.

Abstract: PURPOSE OF REVIEW: To examine the occurrence and pathophysiology of vasculitis in rheumatoid arthritis (RA), describe the epidemiology and clinical features, and provide a therapeutic perspective. RECENT FINDINGS: With improved control of RA over the past two decades, the risk of severe outcomes such as vasculitis may be decreasing. Rheumatoid vasculitis continues to be associated with longstanding, erosive, seropositive disease, and it has recently been shown to be more frequent among patients with antibodies to cyclic citrullinated peptides. Apart from circulating immune complexes, expansion of cytotoxic CD28null T cells and circulating proinflammatory cytokines also play a role in the pathogenesis. The role of agents directed against the tumor necrosis factor (TNF) in the occurrence and management of rheumatoid vasculitis remains unclear, as rheumatoid vasculitis may be both associated with and treated with anti-TNF agents, once it has appeared. SUMMARY: Vasculitis in RA is generally associated with longstanding disease, has an important impact on a patient's well being, and markedly influences patient life expectancy. Advances in therapies for RA will likely continue to reduce the incidence of vasculitis, and improved management of cardiovascular comorbidity in patients with RA will be of particular benefit to those who suffer from vasculitis and other extraarticular manifestations.

Ortendahl M. · Department for Security Research, Royal Institute of Technology, Stockholm, Sweden. · J Eval Clin Pract. · Pubmed #19018900 No free full text.

Abstract: RATIONALE, AIMS AND OBJECTIVES: Diagnostic reasoning and treatment decisions are a key competence of doctors. A model based on values and probability provides a conceptual framework for clinical judgments and decisions, and also facilitates the integration of clinical and biomedical knowledge into a diagnostic decision. METHOD: Both value and probability are usually estimated values in clinical decision making. Therefore, model assumptions and parameter estimates should be continually assessed against data, and models should be revised accordingly. Introducing parameter estimates for both value and probability, which usually pertain in clinical work, gives the model labelled subjective expected utility. Estimated values and probabilities are involved sequentially for every step in the decision-making process. RESULTS: Introducing decision-analytic modelling gives a more complete picture of variables that influence the decisions carried out by the doctor and the patient. CONCLUSION: A model revised for perceived values and probabilities by both the doctor and the patient could be used as a tool for engaging in a mutual and shared decision-making process in clinical work.

Theander E, Jacobsson LT. · Department of Rheumatology, Malmö University Hospital, Lund University, 20502 Malmö, Sweden. · Rheum Dis Clin North Am. · Pubmed #18984413 No free full text.

Abstract: Sjögren's syndrome is a systemic autoimmune disease that frequently presents concomitantly with other systemic connective tissue or organ-specific autoimmune diseases. This association is well described for systemic lupus erythematosus and rheumatoid arthritis. The presence of Sjögren's syndrome influences the expression of the other autoimmune disease to some degree, for instance by increasing fatigue and lymphoma risk. The etiopathogenic mechanism for the simultaneous or sequential development of multiple autoimmune diseases in one individual is not well understood. Common genetic backgrounds and additional immunogenetic, environmental, or hormonal factors may be responsible for the formation of subsets of autoimmune disease clustering. While the most currently accepted classification criteria (American European Consensus Criteria) designate these cases as secondary Sjögrens syndrome, the terms overlapping or associated Sjögren's syndrome are frequently used in the literature to describe these cases.

Lundberg IE, Nader GA. · Rheumatology Unit, Department of Medicine at Karolinska University Hospital, Solna. · Nat Clin Pract Rheumatol. · Pubmed #18839010 No free full text.

Abstract: Exercise is now known to be beneficial for patients with inflammatory rheumatic disease. In patients with rheumatoid arthritis, exercise can improve physical performance, cardiorespiratory fitness and muscle strength, and reduce disease activity and systemic inflammation, as evidenced by reductions in erythrocyte sedimentation rate and other systemic markers of inflammation. Similar effects on physical performance and cardiorespiratory fitness have been observed in patients with polymyositis and dermatomyositis. Improved muscle performance in these patients is associated with an increased ratio of type I : type II muscle fibers and increased cross-sectional area of type II muscle fibers, suggesting that myositis-affected muscle retains the ability to respond to exercise. In addition, resistance exercise training can reduce the expression of genes involved in inflammation and fibrosis in patients with myositis, and in vitro mechanical loading of chondrocytes can suppress the expression of proinflammatory cytokines, indicating that exercise can also reduce inflammation in the local tissue environment. Further studies of the systemic and local responses underlying exercise-associated improvement in muscle performance, soft tissue integrity and health outcomes are warranted.

Turesson C, Jacobsson LT, Matteson EL. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Vasc Health Risk Manag. · Pubmed #18827910 links to  free full text

Abstract: Patients with rheumatic disorders have an increased risk of cardiovascular disease (CVD). This excess co-morbidity is not fully explained by traditional risk factors. Disease severity is a major risk factor for CVD in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease mechanisms in atherosclerosis and rheumatic disorders include immune dysregulation and inflammatory pathways, which are potential targets for therapy. Lessons from RA and SLE may have implications for future research on the pathogenesis of atherosclerotic vascular disease in general. Recent data indicate that suppression of inflammation reduces the risk of CVD morbidity and mortality in patients with severe RA. The modest, but clinically relevant, efficacy of atorvastatin treatment in RA adds to the evidence for important anti-inflammatory properties for statins. There is increased recognition of the need for structured preventive strategies to reduce the risk of CVD in patients with rheumatic disease. Such strategies should be based on insights into the role of inflammation in CVD, as well as optimal management of life style related risk factors. In this review, the research agenda for understanding and preventing CVD co-morbidity in patients with rheumatic disorders is discussed.

Klareskog L, Widhe M, Hermansson M, Rönnelid J. · Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. · Curr Opin Rheumatol. · Pubmed #18388522 No free full text.

Abstract: PURPOSE OF REVIEW: The purpose of this review is to describe how the current knowledge of antibodies to citrullinated protein antigens in rheumatoid arthritis and related conditions emerged; to discuss the diagnostic and prognostic value associated with antibodies to citrullinated protein antigens as a biomarker; and most importantly for this review, to discuss the potential pathogenetic significance of these antibodies. RECENT FINDINGS: Antibodies to citrullinated protein antigens have evolved from being mainly a diagnostic marker, to being recognized as something that can help us understand fundamental etiologic and pathogenetic features of rheumatoid arthritis. Fundamental in this context is the finding that rheumatoid arthritis can be divided into two distinct subsets by means of presence or absence of antibodies to citrullinated protein antigens. Thus, several genetic as well as environmental risk factors differ between these two variants of rheumatoid arthritis. From analysis of these genetic and environmental risk factors, new testable hypotheses have been produced concerning triggering of antibodies to citrullinated protein antigens, and potential pathogenicity of antibodies to citrullinated protein antigens and accompanying immune reactions. SUMMARY: The implications of the findings are that antibodies to citrullinated protein antigens can be used for early and precise diagnosis of a subset of rheumatoid arthritis with worse prognosis than other polyarthritides, and that a new basis is formed for etiologic and pathogenetic studies of antibodies to citrullinated protein antigens-positive rheumatoid arthritis.

Lund I, Lundeberg T. · Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. · Acupunct Med. · Pubmed #18356797 No free full text.

Abstract: Pain is a unique personal experience showing variability where gender and sex related effects might contribute. The mechanisms underlying the differences between women and men are currently unknown but are likely to be complex and involving interactions between biological, sociocultural and psychological aspects. In women, painful experimental stimuli are generally reported to produce a greater intensity of pain than in men. Clinical pain is often reported with higher severity and frequency, longer duration, and present in a greater number of body regions in women than in men. Women are also more likely to experience a number of painful conditions such as fibromyalgia, temporomandibular dysfunction, migraine, rheumatoid arthritis and irritable bowel syndrome. With regard to biological factors, quantitative as well as qualitative differences in the endogenous pain inhibitory systems have been implicated, as well as an influence of gonadal hormones. Psychosocial factors like sex role beliefs, pain coping strategies, and pain related expectancies may also contribute to the differences. Being exposed to repeated painful visceral events (eg menses, labour) during life may contribute to an increased sensitivity to, and greater prevalence of, pain among women. When assessing the outcome of pharmacological and non-pharmacological therapies in pain treatment, the factors of gender and sex should be taken into account as the response to an intervention may differ. Preferably, treatment recommendations should be based on studies using both women and men as the norm. Due to variability in results, findings from animal studies and experiments in healthy subjects should be interpreted with care.

Askling J, Dixon W. · Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska University Hospital and Karolinska Institutet, Solna, Stockholm, Sweden. · Curr Opin Rheumatol. · Pubmed #18349742 No free full text.

Abstract: PURPOSE OF REVIEW: Anti-tumour necrosis factor therapy has proven effective as treatment against a series of autoimmune inflammatory diseases, and has displayed a rapidly increasing market penetration. The safety profile of these drugs is, however, both uncertain and debated, in particular with respect to infections and malignancy. Lack of uniform definitions and methods of analysis makes it difficult to directly compare data from randomized controlled trials, meta-analyses of trials, open-label extensions, data from spontaneous reporting, and particularly, observational cohort studies. RECENT FINDINGS: In this review, we provide a summary of currently published data on infection, malignancy, cardiovascular disease, interstitial lung disease, and death in relation to treatment of rheumatoid arthritis with anti-tumour necrosis factor agents. SUMMARY: Superficially contradictory data on infection display a more or less coherent pattern of an increased risk shortly after treatment starts. Available data on malignancy, cardiovascular disease, interstitial lung disease, and death do not exclude clinically important increased risks, nor do they refute beneficial effects. Harmonized methods of reporting safety data would greatly improve the interpretation and comparison of class and drug-specific risks.

Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L. · Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, SE-171 76, Stockholm, Sweden. · Annu Rev Immunol. · Pubmed #18173373 No free full text.

Abstract: Antibodies to citrullinated proteins (ACPA), i.e., to peptides posttranslationally modified by the conversion of arginine to citrulline, are specific serological markers for rheumatoid arthritis (RA). Studies on anticitrulline immunity, summarized in this review, demonstrate that the criterion-based syndrome RA should be subdivided into at least two distinct subsets (ACPA-positive and ACPA-negative disease). A new etiological model is proposed for ACPA-positive RA, built on MHC class II-dependent activation of adaptive immunity. Fundamentals of this model include the following: (a) ACPA antedate onset of arthritis; (b) ACPA may aggravate arthritis in rodents; (c) ACPA are triggered in the context of genes that confer susceptibility to RA (HLA-DRB1 SE) and by environmental agents triggering RA (smoking or bacterial stimuli); (d) ACPA may complex with citrullinated proteins present in target tissue as part of a multistep process for arthritis development. The model provides a new basis for molecular studies on the pathogenesis of ACPA-positive arthritis.

Kobelt G, Jönsson B. · Department of Orthopedics, University of Lund, Lund, Sweden. · Eur J Health Econ. · Pubmed #18157559 No free full text.

Abstract: Within the series of articles investigating the burden of rheumatoid arthritis (RA), this paper reviews the methods used for economic assessment of the RA treatments by HTA agencies and other bodies involved in cost-effectiveness analysis and the current status of the field. The overall methods, as well as the challenges, of cost-effectiveness analysis in RA are common to all chronic progressive diseases where much of the treatment benefit is delayed, while costs occur immediately. Also, as in all disabling diseases, much of the costs occur outside the health-care system, due to the rapid loss of work capacity and the need for informal care in the later stages of the disease. Thus, it is essential to adopt a long-term view and consider costs from the perspective of society, rather than the health-care service, to increase the relevance of the results for policy making.

Kristensen LE, Christensen R, Bliddal H, Geborek P, Danneskiold-Samsøe B, Saxne T. · Department of Rheumatology, Lund University Hospital, Lund, Sweden. · Scand J Rheumatol. · Pubmed #18092260 No free full text.

Abstract: OBJECTIVE: To compare the efficacy of adalimumab, etanercept, and infliximab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX) by calculating the number needed to treat (NNT) using three different methods. METHODS: A systematic literature search of the Cochrane Library, MEDLINE, and EMBASE was conducted from inception to 30 June 2006. Two pairs of investigators, a Danish and a Swedish pair, independently conducted a structured literature review. The reviewers selected any published randomized, double-blind, MTX controlled study of adalimumab, etanercept, and infliximab, presenting the American College of Rheumatology 50% response (ACR50) after 12 months in RA patients with a mean disease duration of at least 5 years. The two review groups independently extracted the estimates necessary to calculate the NNT. RESULTS: The reviewers consistently selected the same three randomized, controlled trials (RCTs), one for each of the drugs, and extracted equal data for the number of patients completing the 12-month intervention, and the corresponding number of ACR50 responding patients after therapy. Some baseline differences were noted: patients in the etanercept trial had a shorter disease duration and did not receive MTX prior to inclusion; patients in the adalimumab study had lower Health Assessment Questionnaire (HAQ) scores. The calculated NNTs varied slightly depending on the method used. The fully adjusted NNTs (95% confidence intervals) for adalimumab, etanercept, infliximab standard dosage and infliximab double dosage were 4 (3-6), 4 (3-6), 8 (4-66), and 4 (3-11) patients, respectively. CONCLUSION: This study indicates equal efficacy of the three anti-tumour necrosis factor (TNF) therapies.

Kozyrev SV, Alarcon-Riquelme ME. · Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala, Sweden. · Autoimmunity. · Pubmed #18075793 No free full text.

Abstract: Recently much attention was attracted to the importance of the type I interferon pathway in the initiation and development of the autoimmune disease systemic lupus erythematosus (SLE). Many SLE patients have increased serum levels of IFN-alpha and display an IFN gene expression "signature" characterized by strong overexpression of IFN-responsive genes in leukocytes and target tissues. Moreover, about 20% of cancer patients treated with IFN-alpha therapy manifest symptoms resembling SLE and some later develop the disease. One of the key genes of the IFN-alpha pathway, IRF5, was found to be strongly associated with SLE. Two functional SNPs lead to alternative splicing and altered steady-state level of IRF5 gene expression. Besides, the gene has a polymorphic inserion/deletion in exon 6, which contributes to the diversity in the isoform pattern of IRF5. Interestingly, recent studies have not found association of IRF5 with the other autoimmune diseases, such as rheumatoid arthritis or psoriasis, suggesting the unique role for IRF5 in the development of lupus. Here, we present the current knowledge on IRF5 genetics and its biological function and discuss the possible ways in which IRF5 contributes to susceptibility to SLE.

Carlsten H. · Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, Göteborg Academy, Göteborg, Sweden. · Adv Exp Med Biol. · Pubmed #17966392 No free full text.

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Askling J. · Clinical Epidemiology Unit M9:01, Department of Medicine Solna, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. · Curr Rheumatol Rep. · Pubmed #17915099 No free full text.

Abstract: The occurrence of cancer is not an infrequent event in patients with rheumatoid arthritis (RA). Indeed, following diagnosis of RA at a typical age (55 years), one in five patients will be diagnosed with cancer. In the vast majority of such cases, the cancer has nothing to do with RA or its treatment; rather, it represents the "background" risk applicable to all humans. In some cases, the cancer occurs as a result of factors also associated with the risk of developing RA (eg, smoking), even though no direct link exists between the cancer and the RA. In a fraction of cases, however, the cancer is causally associated with the RA disease or its treatments. This review summarizes our current understanding of the occurrence of cancer in RA, possible links to RA disease and to traditional and newer RA treatments.

Okroj M, Heinegård D, Holmdahl R, Blom AM. · Lund University, Department of Laboratory Medicine, University Hospital Malmö, Malmö, Sweden. · Ann Med. · Pubmed #17852027 No free full text.

Abstract: Complement activation contributes to a pathological process in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). In this review we summarize current knowledge of complement contribution to RA, based on clinical observations in patients and in vivo animal models, as well as on experiments in vitro aiming at elucidation of underlying molecular mechanisms. There is strong evidence that both the classical and the alternative pathways of complement are pathologically activated during RA as well as in animal models for RA. The classical pathway can be initiated by several triggers present in the inflamed joint such as deposited autoantibodies, dying cells, and exposed cartilage proteins such as fibromodulin. B cells producing autoantibodies, which in turn form immune complexes, contribute to RA pathogenesis partly via activation of complement. It appears that anaphylatoxin C5a is the main product of complement activation responsible for tissue damage in RA although deposition of membrane attack complex as well as opsonization with fragments of C3b are also important. Success of complement inhibition in the experimental models described so far encourages novel therapeutic approaches to the treatment of human RA.

Holmdahl R. · Medical Inflammation Research, I11 BMC, Lund University, 22184 Lund, Sweden. · Ernst Schering Found Symp Proc. · Pubmed #17824178 No free full text.

Abstract: Inflammation is a physiological response that may go uncontrolled and thereby develop in a chronic way. This seems to happen in many common diseases of autoimmune, degenerative, or allergic character. Rheumatoid arthritis (RA) is by definition a chronic disease with an autoimmune inflammatory attack on diarthrodial cartilaginous joints. The development of new treatment neutralizing cytokines involved in the inflammatory attack has given relief and gives the promise of more effective treatment of already established disease. It is now time to set our eyes on a new vision to develop preventive and curative treatment based on knowledge of the unique and causative pathogenic mechanisms. To do this we believe it is important to identify the natural-selected polymorphisms that are associated with disease. These have proven to be extremely difficult to identify in complex diseases such as RA, but using animal models, this work is closer to reality. Animal models have recently been developed mimicking various aspects of the human disease. We will present an example in which a genetic polymorphism associated with the development of arthritis has been identified. On the basis of this finding, a new pathway involving control of immune tolerance by reactive oxidative species has been identified and a new class of antiinflammatory agents activating the induced oxidative burst protein complex is suggested.

Sun XF, Zhang H. · Department of Oncology, Institute of Biomedicine and Surgery, University of Linköping, Linköping, Sweden. · Histol Histopathol. · Pubmed #17701919 No free full text.

Abstract: Nuclear factor-kappaB (NF-kappaB) is responsible for the expression by regulating many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis and apoptosis. The function of NF-kappaB is inhibited by binding to NF-kappaB inhibitor (IkappaB), and imbalance of NF-kappaB and IkappaB has been associated with development of many diseases, including tumours. In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.

Gelderman KA, Hultqvist M, Olsson LM, Bauer K, Pizzolla A, Olofsson P, Holmdahl R. · Unit for Medical Inflammation Research, Department of Experimental Medical Science, Lund University, Lund, Sweden. · Antioxid Redox Signal. · Pubmed #17678439 No free full text.

Abstract: Autoimmune diseases such as rheumatoid arthritis (RA) are chronic diseases that cannot be prevented or cured If the pathologic basis of such disease would be known, it might be easier to develop new drugs interfering with critical pathway. Genetic analysis of animal models for autoimmune diseases can result in discovery of proteins and pathways that play key function in pathogenesis, which may provide rationales for new therapeutic strategies. Currently, only the MHC class II is clearly associated with human RA and animal models for RA. However, recent data from rats and mice with a polymorphism in Ncf1, a member of the NADPH oxidase complex, indicate a role for oxidative burst in protection from arthritis. Oxidative burst-activating substances can treat and prevent arthritis in rats, as efficiently as clinically applied drugs, suggesting a novel pathway to a therapeutic target in human RA. Here, the authors discuss the role of oxygen radicals in regulating the immune system and autoimmune disease. It is proposed that reactive oxygen species set the threshold for T cell activation and thereby regulate chronic autoimmune inflammatory diseases like RA. In the light of this new hypothesis, new possibilities for preventive and therapeutic treatment of chronic inflammatory diseases are discussed.

Nilsson BO. · Department of Experimental Medical Science, Division of Vascular and Airway Research, Unit of Vascular Physiology, Lund University, BMC D12, 221 84 Lund, Sweden. · Inflamm Res. · Pubmed #17659431 No free full text.

Abstract: Gender differences and variations in inflammatory disease (e. g. atherosclerosis, neurological disorders, periodontitis and rheumatoid arthritis) severity with female sex hormone level have been reported, suggesting that female sex hormones modulate the inflammatory response. Estrogens act on gene transcription via estrogen receptors alpha and beta. Identification of estrogen-regulated genes is a matter of great interest since it will contribute significantly to the understanding of the physiological importance of estrogens. Anti-inflammatory as well as pro-inflammatory responses to estrogens have been reported. Data have been presented showing that estrogens down-regulate the expression of adhesion and chemokine molecules in response to inflammation promoters in various experimental systems. Functional data show that estrogen treatment attenuates recruitment and adhesion of leukocytes to the endothelium induced by inflammation promoters offering a possible mechanism by which estrogens exert an anti-inflammatory effect. These effects of estrogens, with focus on the interactions of monocytes with the vascular endothelium, are highlighted in this review.

Bokarewa M, Tarkowski A, Magnusson M. · Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, Göteborg University, S-41346 Göteborg, Sweden. · Scand J Immunol. · Pubmed #17635796 No free full text.

Abstract: Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage and bone destruction. Insufficient apoptosis in the inflamed RA synovium along with accumulation of highly differentiated B- and T-lymphocytes as well as invasive growth of macrophages and fibroblasts is among the major mechanisms supporting joint destruction. We have recently shown that circulating survivin, an apoptosis inhibitor tightly bound to tumorigenesis, is an independent predictor of development and progression of joint destruction in RA. In this review we discuss the possible connectivity between viral infection, leading to interferon (IFN)-alpha production, survivin expression, and subsequent joint inflammation. The role of IFN-alpha and the involvement of IFN transcription factors and phosphoinositide-3-kinase signalling as essential modulators of arthritogenic process are discussed in the context of survivin.

von Bültzingslöwen I, Sollecito TP, Fox PC, Daniels T, Jonsson R, Lockhart PB, Wray D, Brennan MT, Carrozzo M, Gandera B, Fujibayashi T, Navazesh M, Rhodus NL, Schiødt M. · Department of Oral Medicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. <> · Oral Surg Oral Med Oral Pathol Oral Radiol Endod. · Pubmed #17379156 No free full text.

Abstract: OBJECTIVES: The objective of this study was to identify systemic diseases associated with hyposalivation and xerostomia and develop evidence-based management recommendations for hyposalivation/xerostomia. STUDY DESIGN: Literature searches covered the English language medical literature from 1966 to 2005. An evidence-based review process was applied to management studies published from 2002 to 2005. RESULTS: Several systemic diseases were identified. From studies published 2002 to 2005, 15 were identified as high-quality studies and were used to support management recommendations: pilocarpine and cevimeline are recommended for treating hyposalivation and xerostomia in primary and secondary Sjögren's syndrome (SS). IFN-alpha lozenges may enhance saliva flow in primary SS patients. Anti-TNF-alpha agents, such as infliximab or etanercept, are not recommended to treat hyposalivation in SS. Dehydroepiandrosterone is not recommended to relieve hyposalivation or xerostomia in primary SS. There was not enough evidence to support any recommendations for the use of local stimulants, lubricants, and protectants for hyposalivation/xerostomia. However, professional judgment and patient preferences may support the use of a specific product for an individual patient. CONCLUSIONS: These evidence-based management recommendations should guide the clinician's management decisions for patients with salivary dysfunction related to systemic disease. Future treatment strategies may include new formulations of existing drugs, e.g., local application of pilocarpine. Recent discoveries on gene expression and a better understanding of the etiopathogenesis of SS may open new treatment options in the future.

Kobelt G. · Lund University, Lund, Sweden. · Scand J Rheumatol. · Pubmed #17343248 No free full text.

Abstract: The objectives of treatment in rheumatoid arthritis (RA) are to reduce temporary symptoms due to inflammatory activity and, more importantly, to preserve function. The introduction of potent disease-modifying anti-rheumatic drugs (DMARDs) in recent years has increased the opportunities for effective treatment. However, these treatments come at a substantially higher cost than traditional DMARDs and therefore compete with other essential interventions for limited resources. They have triggered a debate on whether they represent an efficient use of resources, which patients should be treated, when, and for how long. Cost-effectiveness analysis attempts to estimate the trade-offs involved in these decisions and to provide information that can help in making them. However, in chronic progressive diseases, health gains and any potential associated economic benefits are often most evident in the long-term. As a consequence, the impact of new treatments has to be estimated using models that can project available knowledge, such as results from clinical trials or short-term follow-up studies in clinical practice, into the future. These models also allow scenarios to be explored that provide the best value for money, for example by defining subgroups for which treatment is most effective, or criteria that define when treatment should be stopped. Economic evaluation in RA has a long tradition, with the first study performed about 20 years ago. However, with the recent drug introductions, the field has witnessed an explosion of economic studies. Modelling techniques have become more sophisticated to overcome concerns about their validity. At the same time, they may appear less transparent, making it difficult for non-specialists to understand the details. This article, rather than reviewing all published models and comparing them, attempts to illustrate the inputs required for such studies, and the influence that different approaches and datasets can have on the results.