IL-10 production is enhanced in human T cells by IL-12 and IL-6 and in monocytss by tumor necrosis factor-α

IL-10, an immunoregulatory cytokine produced by T cells and monocytes, inhibits the expression of inflammatory and haematopoietic cytokines as well as its own expression. To evaluate the regulation of IL-10 production by T cells and monocytes, we measured IL-10 levels in supernatants of PHA stimulated PBMC following depletion of either T cells or monocytes. IL-10 production was significantly downregulated in monocyte depleted PBMC compared to undepleted PBMC, and IL-10 production could be restored following addition of monocyte conditioned medium {MCM) . To clarify the monokine(s) responsible for IL-10 induction, we stimulated monocyte depleted PBMC, purified CD4+ and CD8 + T cells with PHA and measured IL-10 production by ELISA and semiquantitative RTPCR following monokine(s) addition. Addition of IL-6 and IL12 enhanced IL-10 production by these cells in a dose dependent and additive manner. Furthermore, anti-IL-6 and anti-IL-12 antibodies neutralized the IL-10 inductive effect of MCM. With respect to regulation of IL-10 produced by monocytes, TNF-a was found to induce IL-10 production by resting as well as LPS stimulated purified monocytes/ macrophages. Since IL-10 inhibits production of IL-6, IL-12 and TNF-a, these results indicate a potential mechanism of negative feedback regulation of the immune response. This work was supported by grants from the Research Institute, CHEO and CANFAR, Canada.