T helper 2 cytokines differently regulate monocyte chemoattractant protein-1 production by human peripheral blood monocytes and alveolar macrophages

Abstract

Th2 cytokines, such as IL-4, IL-10, and IL-13, suppress proinflammatory cytokine production by monocytes/macrophages. Since monocyte chemoattractant protein-1 (MCP-1) is presumed to play an important role in monocyte recruitment and activation during inflammatory and immune responses, we examined here the effects of these Th2 cytokines on MCP-1 production by human blood monocytes and alveolar macrophages. Unstimulated, highly purified blood monocytes did not produce MCP-1 spontaneously, while LPS treatment induced the production of MCP-1 and its mRNA expression. All Th2 cytokines tested suppressed LPS-induced MCP-1 production and its mRNA expression, although the suppressive effect of IL-13 was weaker than that of IL-4 or IL-10. In contrast, IL-10, but neither IL-4 nor IL-13, induced unstimulated peripheral blood monocytes to produce biologically active MCP-1 protein within 4 h, reaching a maximal level at 12 h. IL-10-induced MCP-1 production was reduced by pretreatment of IL-10 with anti-IL-10 Ab, negating the involvement of contaminated endotoxin. Moreover, IL-10 induced MCP-1 mRNA expression in unstimulated monocytes, independent of de novo protein synthesis. Furthermore, human alveolar macrophages produced MCP-1 spontaneously, and the production was inhibited by IL-4 or IL-13, but was augmented by IL-10. These findings suggest that IL-10 regulates MCP-1 production by monocytes/macrophages in a different way from other Th2 cytokines, such as IL-4 and IL-13, and contributes to host defense responses.