CROSS-REGULATORY ROLES OF INTERLEUKIN (IL)-12 AND IL-10 IN ATHEROSCLEROSIS

T cell cytokines are known to play a major role in determining protect ion and pathology in infectious disease. It has recently become clear that IL-12 is a key inducer of the type 1 T cell cytokine pattern char acterized by production of IFN-gamma. Conversely, n-10 down-regulates IL-12 production and type 1 cytokine responses. We have investigated w hether IL-12 and IL-10 might be involved in a chronic inflammatory rea ction, atherosclerosis. In atherosclerotic plaques, we found strong ex pression of IFN-gamma but not IL-4 mRNAs as compared to normal arterie s. IL-12 p40 mRNA and IL-12 p70 protein were also found to be abundant in atherosclerotic plaques. IL-12 was induced in monocytes in vitro i n response to highly oxidized LDL but not minimally modified LDL. The cross-regulatory role of IL-10 was indicated by the expression of IL-1 0 in some atherosclerotic lesions, and the demonstration that exogenou s rIL-10 inhibited LDL-induced IL-12 release. These data suggest that the balance between IL-12 and IL-10 production contributes to the leve l of immune-mediated tissue injury in atherosclerosis.