Resistin Gene Expression is Downregulated in CD4 super(+) T Helper Lymphocytes and CD14 super(+) Monocytes in Rheumatoid Arthritis Responding to TNF- alpha 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- alpha 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- gamma , TNF- beta , IL-1 beta , TNF- alpha , TGF- beta and IL-10 gene expressions in CD14 super(+) monocytes, CD4 super(+) T helper (Th) lymphocytes (ly), CD8 super(+) T cytotoxic (Tc) ly and CD19 super(+) B ly in active RA before and 3 months after start of TNF- alpha I. 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- alpha I caused a significant downregulation of RETN gene expression in CD14 super(+) monocytes and CD4 super(+) Th ly and was unchanged in CD8 super(+) Tc ly and CD19 super(+) B ly. Both in active RA and during TNF- alpha I, RETN mRNA levels were significantly higher in CD14 super(+) monocytes than in all other examined cell types. In monocytes, fold change in RETN and TGF- beta gene expressions upon TNF- alpha I correlated significantly. Our findings indicate that RETN has pro-inflammatory as well as proresolving roles in active RA.