IL-4 enhances programmed cell death (apoptosis) in stimulated human monocytes.
Because IL-4 down-regulates several proinflammatory functions associated with human monocytes/macrophages, we explored the possibility that IL-4 also decreases monocyte survival. IL-4 caused a concentration-dependent decrease in viability of IL-1 or LPS stimulated, but not unstimulated, monocytes. Nonviable cells demonstrated classic features of programmed cell death or apoptosis, in that they were condensed and contained oligonucleosome-sized (200 bp) DNA fragments. When compared with several other cytokines commonly associated with inflammatory lesions, IL-4 was uniquely effective in enhancing cell death. We found that IL-4 enhanced death more quickly in IL-1-stimulated cells than in LPS-stimulated cells, that stimulated monocytes did not become resistant to the effects of IL-4 during culture, and that the effects of IL-4 on viability were antagonized by IFN-gamma. Enhanced cell death was stimulus-specific in that monocyte viability maintained by certain activating agents, such as Con A or CSF, was unaffected by IL-4. These findings represent the first evidence of cytokine-enhanced programmed cell death in monocytes and suggest that the antiinflammatory effects of IL-4 are mediated in part by reducing survival of stimulated monocytes in chronic lesions.
Mangan
D F
DF
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Robertson
B
B
Wahl
S M
SM
D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004249:DNA Damage; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007371:Interferon-gamma