Melanocortin 2, 3 and 4 Receptor Gene Expressions are Downregulated in CD8⁺ T Cytotoxic Lymphocytes and CD19⁺ B Lymphocytes in Rheumatoid Arthritis Responding to TNF‐α Inhibition

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 ( MC 1‐5R) 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. CD 4 + T helper (h) lymphocytes (ly), CD 8 + T cytotoxic (c) ly, CD 19 + B ly and CD 14 + monocytes were isolated, using immunomagnetic beads, total RNA extracted and reverse transcription quantitative polymerase chain reaction ( RT ‐ qPCR ) performed. Fold changes in MC 1‐5R, 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, MC 1‐5R gene expressions decreased in responders and increased in the non‐responder. In responders, decrease in MC 2R, MC 3R and MC 4R gene expressions in CD 8 + Tc and CD 19 + B ly was significant. Fold change in MC 1‐5R and IFN γ gene expressions correlated significantly in CD 8 + Tc ly, while fold change in MC 1R, MC 3R and MC 5R and IL ‐1 β gene expressions correlated significantly in CD 4 + Th ly. Our results show regulation of MC 2R, MC 3R and MC 4R gene expressions in CD 8 + Tc ly and CD 19 + B ly. The correlations between fold change in different MCR s and disease driving cytokine gene expressions in CD 8 + Tc ly and CD 4 + Th ly point at a central immune modulating function of the melanocortin system in RA .