Rheumatoid Arthritis: Pejnovic N

Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D, Pavlica L, Stefanovic D. · Department of Rheumatology, Military Medical Academy, Belgrade, Yugoslavia. · Clin Exp Rheumatol. · Pubmed #10464556 No free full text.

Abstract: OBJECTIVE: Vitamin D analogues such as 1 alpha (OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differentiation. Experimentally established possibilities to prevent autoimmune diseases suggest that alphacalcidiol may have therapeutic value as an immunomodulatory agent in patients with rheumatoid arthritis. METHODS: We organized a 3-month open-label trial on 19 patients being treated with standard DMARD therapy for acute RA. They were divided into 2 subgroups, those with highly active RA and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidiol 2 micrograms/day was added. Therapy results were evaluated by ESR, CRP, morning stiffness, the Richie index, and the Lee index. Immunomodulatory effects were investigated by measuring lymphocyte proliferation and apoptosis both in the patients and in vitro in 10 nM alphacalcidiol-supplemented culture medium. RESULTS: After 3 months, high dose oral alphacalcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or 9 pts. with complete remission and 44% or 8 pts. with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side effects were observed. CONCLUSION: These results suggest that alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent. We noticed dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state. Alphacalcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with rheumatoid arthritis.

Petrovic-Rackov L, Pejnovic N. · Clinic of Rheumatology and Clinical Immunology, Military Medical Academy, Belgrade, Serbia and Montenegro. · Clin Rheumatol. · Pubmed #16362448 No free full text.

Abstract: The aim of the study was to evaluate the clinical significance of serum (S) and synovial fluid (SF) interleukin (IL)-18, IL-15, IL-12 and the tumor necrosis factor alpha (TNF-alpha) measurements in relation to laboratory and clinical measures of disease activity of patients with active rheumatoid arthritis (RA). Sixty-four patients with RA and 25 patients with osteoarthritis (OA) were included in this study. RA activity was determined using the Disease Activity Score (DAS) 28 index. Concentrations of IL-18, IL-15, IL-12 and TNF-alpha were measured by ELISA. Serum C-reactive protein (CRP) levels were also determined. Cross-sectional correlations between S and SF levels of cytokines and values of DAS 28 index were calculated. The results have shown that IL-18, IL-15, IL-12 and TNF-alpha levels in S and SF of patients with RA were significantly higher than the levels obtain from patients with OA (p<0.01). Significantly higher levels of IL-18, IL-15 and TNF-alpha were found in the SF compared to the S of patients with RA (p<0.01). Significantly higher S and SF levels of all four cytokines and serum CRP values were found in RA patients with high disease activity (DAS 28>5.1) compared to those with mild (DAS 28>3.2) and low disease activity (DAS 28>2.6) (p<0.01). Serum and SF concentrations of all four cytokines positively correlated with DAS 28 index values, i.e., disease activity. A poor correlation was found for S and SF IL-12 whereas the highest coefficient of correlation was found for SF IL-18 (r=0.879, p<0.01), and SF TNF-alpha (r=0.827, p<0.01) and disease activity in this study. Strong correlation was found between SF TNF-alpha and SF IL-18 levels (r=0.732, p<0.01). In conclusion, SF IL-18 and TNF-alpha levels in RA patients are good indicators of disease activity. The results obtained support the use of the DAS in clinical practice as a reliable method in assessing disease activity in RA patients.

Vujasinovic-Stupar N, Pejnovic N, Markovic O, Babic G. · No affiliation provided · Ann Hematol. · Pubmed #18386008 No free full text.

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