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Melanocortin signalling in leucocyte subsets elicits anti-inflammatory and immune tolerance inducing effects in animal experimental inflammation. In man, however, the effects of melanocortin signalling in inflammatory conditions have scarcely been examined. We explored the differential reactions of melanocortin 1-5 receptors ( MC1-5R) gene expressions in pathogenetic leucocyte subsets in rheumatoid arthritis ( RA) to treatment with TNF- α inhibitor adalimumab. Seven patients with active RA donated blood at start and at 3-month treatment. CD4+ T helper (h) lymphocytes (ly), CD8+ T cytotoxic (c) ly, CD19+ B ly and CD14+ monocytes were isolated, using immunomagnetic beads, total RNA extracted and reverse transcription quantitative polymerase chain reaction ( RT- qPCR) performed. Fold changes in MC1-5R, Th1-, inflammatory- and regulatory cytokine gene expressions were assessed for correlation. Six patients responded to adalimumab treatment, while one patient was non-responder. In all lymphocyte subtypes, MC1-5R gene expressions decreased in responders and increased in the non-responder. In responders, decrease in MC2R, MC3R and MC4R gene expressions in CD8+ Tc and CD19+ B ly was significant. Fold change in MC1-5R and IFN γ gene expressions correlated significantly in CD8+ Tc ly, while fold change in MC1R, MC3R and MC5R and IL-1 β gene expressions correlated significantly in CD4+ Th ly. Our results show regulation of MC2R, MC3R and MC4R gene expressions in CD8+ Tc ly and CD19+ B ly. The correlations between fold change in different MCRs and disease driving cytokine gene expressions in CD8+ Tc ly and CD4+ Th ly point at a central immune modulating function of the melanocortin system in RA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis ( RA) is caused by complex interactions between immune cells and sustained by Th1 response cytokines. Resistin [resistance to insulin; (RETN)] is an inflammatory cytokine, first discovered in murine adipocytes. In man, RETN is mainly secreted by monocytes. The distinct role of RETN in the immune reaction is uncertain; however, RETN has pro-inflammatory, pro-fibrotic and possibly tolerogenic properties. The aim was to assess the reaction of RETN gene expression to TNF- α inhibition (I) in pathogenetic immune cell subsets in RA, in the context of Th1, inflammatory and regulatory cytokine gene expressions. Accordingly, we measured RETN, IFN- γ, TNF- β, IL-1 β, TNF- α, TGF- β and IL-10 gene expressions in CD14+ monocytes, CD4+ T helper (Th) lymphocytes (ly), CD8+ T cytotoxic (Tc) ly and CD19+ B ly in active RA before and 3 months after start of TNF- αI. Leucocyte subsets were separated by specific monoclonal antibody-covered beads, RNA extracted and levels of RETN, Th1 response, inflammatory and regulatory cytokine mRNAs measured by quantitative reverse transcription-polymerase chain reaction technique. We found that TNF- αI caused a significant downregulation of RETN gene expression in CD14+ monocytes and CD4+ Th ly and was unchanged in CD8+ Tc ly and CD19+ B ly. Both in active RA and during TNF- αI, RETN mRNA levels were significantly higher in CD14+ monocytes than in all other examined cell types. In monocytes, fold change in RETN and TGF- β gene expressions upon TNF- αI correlated significantly. Our findings indicate that RETN has pro-inflammatory as well as proresolving roles in active RA. [ABSTRACT FROM AUTHOR]