Interleukin (IL)-10 inhibits RANTES-, tumour necrosis factor (TNF)- and nerve growth factor (NGF)-induced mast cell migratory response but is not a mast cell chemoattractant

Abstract

Interleukin (IL)-10 is an important immunoregulatory cytokine with multiple biologic effects on different cell types. This cytokine also affects mast cell development, survival and activity. Mast cells are well known for their role in diverse pathophysiological processes including inflammatory events. Mast cell number in tissues is high and relatively constant. However, it is well established that these cells accumulate at the sites of inflammation in response to chemoattractants, e.g. RANTES, tumour necrosis factor (TNF) and nerve growth factor (NGF). In the present study, we examined whether IL-10 influenced RANTES-, TNF- and NGF-induced rat peritoneal mast cell migration. We also studied whether IL-10 could act as mast cell chemoattractant. We provided evidence, for the first time ever, that IL-10 influenced mature mast cell migration, i.e. it strongly decreased RANTES-induced mast cell migration and completely inhibited mast cell migratory response to TNF and NGF. The effective concentration of IL-10 that inhibited RANTES-, TNF- and NGF-induced mast cell migratory response was in the nanomolar range. The inhibitory effect of IL-10 on cytokine-stimulated mast cell migration was specific, as it was completely blocked by anti-IL-10R antibodies, and STAT3-dependent. In addition, our results have shown that IL-10 was not a mast cell chemoattractant. Thus, our findings clearly demonstrated that IL-10 may affect mast cell number within tissue by inhibiting local mast cell accumulation stimulated by chemotactic factors.