Rheumatoid Arthritis: Cipriani P

Giacomelli R, Cipriani P, Matucci Cerinic M, Fulminis A, Barattelli G, Pingiotti E, Di Franco M, Trotta A, Perricone R, Zazzeroni F, Alesse E, Tonietti G. · Clinica Medica, University of L'Aquila, Italy. · Clin Exp Rheumatol. · Pubmed #12102473 No free full text.

Abstract: OBJECTIVE: To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA). METHODS: 24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR. RESULTS: 10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy. CONCLUSION: The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.

Pingiotti E, Cipriani P, Marrelli A, Liakouli V, Fratini S, Penco M, Giacomelli R. · Department of Internal Medicine and Public Health, University of L'Aquila, Via Vetoio, Coppito, L'Aquila 67100, Italy. · Ann N Y Acad Sci. · Pubmed #17804530 No free full text.

Abstract: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. Fractalkine, a CX3C/chemokine (CX3CL1), mediates monocytes-macrophage infiltration in activated endothelium, suggesting its specific role in atherosclerosis-related inflammation. In this study, we evaluate the following in early RA patients: the expression of fractalkine receptor (CX3CR1) on CD4+/CD28- T cells, a subset involved in atherosclerotic infiltration; the correlation between this subset and validated markers of early atherosclerosis. CD4+ T cells were isolated by immunomagnetics beads in 50 early RA patients and 26 healthy controls (HC). After isolation, CD4+/CD28-/CX3CR1+ T lymphocytes were assessed by FACS analysis. Endothelial dysfunction was evaluated by both carotid intima-media thickness (IMT) and flow-mediated vasodilation (FMV). We observed: a higher expansion of CD4+/CD28- subset in RA patients when compared to HC (7.7%, 5.15-9.7 vs. 0.7%, 0.2-1.5, P < 0.01; respectively); this expansion directly correlated with increased IMT (0.91 mm, 0.5-1.3 vs. 0.7 mm, 0.2-1, P < 0.01; RA vs. C, respectively) and inversely correlated with FMV (3.5%, 1.7-7 vs. 9%, 3.5-11, P < 0.01; RA vs. C, respectively); the large majority of CD4+/CD28-, in RA, coexpressed CX3CR1 (93%, 67-99 vs. 30%, 10-48, P < 0.01; RA vs. C, respectively); this expansion significantly correlated with both the parameters of premature vascular damage and DAS 28. Our data suggest that CX3CL1/CX3CR1 axis might play a role in the induction and development of the endothelial dysfunction during RA.