Interleukin-10 inhibits interleukin-8 production in human neutrophils

Abstract

In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL- 6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.

Expression of genes associated with inflammation induced by ex vivo exposure to lipopolysaccharide in peripheral blood leukocytes from horses with gastrointestinal disease

“…An anti-inflammatory cytokine, IL-10, is produced primarily by monocytes and, to a lesser extent, by lymphocytes. 20,30 This cytokine suppresses the synthesis of proinflammatory cytokines [30][31][32] and is one of the principal modulators of the inflammatory response. 33,34 In peripherally obtained blood from septic humans, an increase in plasma concentration and leukocyte expression of IL-10 is associated with immunosuppression and a poor prognosis.…”