Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migration "in vivo" by indirect mechanisms.
The alpha and beta forms of recombinant interleukin-1 (IL-1 alpha and IL-1 beta) and of recombinant Tumor Necrosis Factor (TNF alpha and TNF beta) induced dose-dependent neutrophil migration into rat peritoneal cavities. Migration induced by both IL-1s showed a bell-shaped dose-response curve and IL-1 beta was 3-fold more potent than IL-1 alpha. Pretreatment of the animals with dexamethasone or depletion of the peritoneal macrophage population, abolished the neutrophil migration induced by the four cytokines. "In vitro" stimulation of macrophage monolayers with IL-1 beta and the TNFs released a factor into the supernatant which, unlike these cytokines, induced neutrophil migration in dexamethasone pretreated animals. These results suggest that the neutrophil migration induced by IL-1 alpha, IL-1 beta, TNF alpha and TNF beta is not due to a direct effect on neutrophils, but occurs via the release of a chemotactic factor(s) from resident macrophages.
Department of Pharmacology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
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D000818:Animals; D002464:Cell Migration Inhibition; D002630:Chemotactic Factors / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology*; D016209:Interleukin-8; D008070:Lipopolysaccharides / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D002630:Chemotactic Factors; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha