EFFECT OF INTERLEUKIN-4 AND INTERLEUKIN-10 ON LEUKOCYTE MIGRATION AND NITRIC-OXIDE PRODUCTION IN THE MOUSE

1 The effect of systemic treatment of mice with murine recombinant interleukin-4 (IL-4) or interleukin-10 (IL-10) on neutrophil infiltration into a specific tissue site and nitric oxide (NO) production from peritoneal macrophages was investigated. 2 2 Intravenously (i.v.) administered IL-4 (0.01-10 mu g per mouse, approximately 0.3-300 mu g kg(-1), i.v.) and IL-10 (0.01-1 mu g per mouse, approximately 0.3-30 mu g kg(-1), i.v.) dose-dependently inhibited neutrophil accumulation into a 6-day-old murine air-pouch induced by local application of interleukin-1 beta (IL-1 beta, 5 ng), with approximate ED(50)s of 0.35 and 0.90 mu g, respectively. Neither IL-4 (1 mu g, 30 mu g kg(-1), i.v.) nor IL-10 (1 mu g, 30 mu g kg(-1), i.v.) prevented leucocyte accumulation in the mouse air-pouches when interleukin-8 (IL-8, 1 mu g) was used as chemoattractant. Similarly, neither cytokine had any effect on the in vitro up-regulation of CD11b antigen on the surface of murine circulating neutrophils. 3 Treatment of mice with lipopolysaccharide (LPS, 0.3 mg kg(-1), i.p.) caused an increase in the formation of NO (measured as nitrite accumulation) in the supernatant of peritoneal macrophages ex vivo. Pretreatment of mice with IL-4 (0.01-1 mu g i.v., 20 min before LPS), but not with IL-10 (1 mu g i.v., 20 min before LPS), caused a dose-dependent reduction in this LPS-stimulated formation of nitrite by peritoneal macrophages ex vivo. 4 Activation of murine macrophages with LPS (1 mu g ml(-1) for 24 h) in vitro caused a significant increase in nitrite release in the supernatant of these cells. Pretreatment of either J774.2 or peritoneal macrophages with IL-4 (0.1-1 mu g ml(-1), 20 min before LPS), but not with IL-IO (1 mu g ml(-1), 20 min before LPS) caused a concentration-related attenuation of this LPS-stimulated nitrite formation. 5 Thus, both IL-4 and IL-10 inhibit the migration of leucocytes (stimulated by IL-1 beta) in vivo; IL-4 (but not IL-10) inhibits the induction of NO synthase caused by LPS in murine macrophages in vitro and ex vivo.