Interleukin‐10 Directly Inhibits the Interleukin‐6 Production in T‐Cells

IL‐6 is a potent regulator of T‐cell activation, proliferation and differentiation. Since IL‐10 inhibits cytokine production by T cells, the effect of IL‐10 on IL‐6 production by T cells was investigated. IL‐6 production by purified monocytes or T cells was detected from cell‐free culture supernatants by ELISA after stimulation of the cells with LPS or an anti‐CD3 monoclonal antibody for 3 days. Although the main source of IL‐6 are LPS activated monocytes (29.6 × lOng/ml), T cells secreted sufficiently high levels of IL‐6 (790 × 200pg/ml) to stimulate the high affinity IL‐6 receptor. IL‐10 decreased anti‐CD3 induced IL‐6 mRNA expression by up to 80%. In addition, IL‐10 significantly inhibited IL‐6 release from T‐cells. Highly purified, anti‐CD3 activated T‐cells secreted 600 × 150pg/ml IL‐6 compared to 21 × 2pg/ml IL‐6 following addition of IL‐10 (10ng/ml; P <0.001). FACS analysis revealed a monocyte contamination of the T‐cell preparations of less than 0.5%. In addition, no IL‐1 production was detectable. Thus, in our experiments the effect of TL‐10 on IL‐6 production was independent of the presence of monocytes. Finally, inhibition of IL‐6 production was not reversed by IL‐2 (100U/ml). In conclusion, IL‐10 suppressed the synthesis of IL‐6 by T‐cells via a monocyte‐and IL‐2‐independeni mechanism. These results may help to understand the complex regulation of T‐cell mediated cytokine production by IL‐10.