IL-4 and IL-13 modulate IL-10 release in endotoxin-stimulated murine peritoneal mononuclear phagocytes.
Several recent reports presented conflicting data on the action of IL-4 and IL-13 in regulating the release of proinflammatory cytokines by human monocytes. Here we show that the regulation of cytokine release by IL-4 and IL-13 could be either inhibitory or stimulatory in LPS-treated murine peritoneal macrophages. When macrophages were treated with IL-13 or IL-4, between 6 and 24 hr prior to endotoxin challenge, TNF alpha and IL-6 levels were significantly augmented. On the other hand, when the cells were cotreated with LPS plus IL-13 or IL-4, the release of TNF alpha and IL-6 was inhibited. These effects of IL-4 and IL-13 were associated with the modulation of IL-10; pretreatment resulted in a decrease, whereas cotreatment gave rise to a dramatic increase in IL-10 levels. The inhibitory effect of IL-4 and IL-13 on the release of TNF alpha was partially reversed by neutralizing anti-IL10 antibody, and the inhibition of IL-6 release was completely reversed by the antibody. These data suggest that the mechanism of action of IL-13 and IL-4 in modulating macrophage TNF alpha and IL-6 release partially involves IL-10.
Kambayashi
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Department of Immunology, Otsuka-America Pharmaceutical Inc., Rockville, Maryland 20850, USA.
Jacob
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CO
Strassmann
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000276:Adjuvants, Immunologic; D018793:Interleukin-13; D008070:Lipopolysaccharides; D016753:Interleukin-10; D015847:Interleukin-4