Resistin Gene Expression is Downregulated in CD4+ T Helper Lymphocytes and CD14+ Monocytes in Rheumatoid Arthritis Responding to TNF- α Inhibition.

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]