IL-10 AS AN AUTOCRINE REGULATOR OF CSF SECRETION BY MONOCYTES - DISPARATE EFFECTS ON GM-CSF AND G-CSF SECRETION

In previous studies of endogenous granulocyte-macrophage colony-stimul ating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF ) production, we found several differences in the secretion pattern wi thin and between different cell systems; for example, CSF secretion by endothelial cells is not affected by any major downregulatory factors , whereas monocyte CSF secretion is modulated by several mechanisms. I n this study, we characterized the factors that inhibit CSF secretion by monocytes. Three cytokines have inhibitory effects: interleukin (IL )-4, IL-10, and IL-13. Among these, IL-4 and IL-10 have higher potency than IL-13. IL-4 and IL-13 affect GM-CSF and G-CSF secretion to the s ame extent. In contrast, exogenously added IL-10 has a stronger inhibi tory effect on GM-CSF secretion than on G-CSF secretion. We also found that monocytes produce IL-10 with an autocrine downregulatory effect, and that this autocrine IL-10 reaches concentrations at which in most cases only GM-CSF (not G-CSF) secretion is significantly affected. We postulate that the disparate effect of IL-10 on monocyte secretion of the two CSFs reflects their physiological functions, with GM-CSF bein g mainly a proinflammatory cytokine working in the local compartment a nd G-CSF functioning mainly as a cell recruiting factor.