RECOMBINANT INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR INDUCE NEUTROPHIL MIGRATION INVIVO BY INDIRECT MECHANISMS

The α and β forms of recombinant interleukin-1 (IL-1α and IL-1β) and of recombinant Tumor Necrosis Factor (TNFα and TNFβ) induced dose-dependent neutrophil migration into rat peritoneal cavities. Migration induced by both IL-1s showed a bell-shaped dose-response curve and IL-1β was 3-fold more potent than IL-1α. 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-1β 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-1α, IL-1β and TNFβ is not due to a direct effect on neutrophils, but occurs via the release of a chemotactic factors(s) from resident macrophages. © 1990 Birkhäuser Verlag.