Effect of interleukin-4 and interleukin-10 on leucocyte 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. Intravenously (i.v.) administered IL-4 (0.01-10 micrograms per mouse, approximately 0.3-300 micrograms kg-1, i.v.) and IL-10 (0.01-1 micrograms per mouse, approximately 0.3-30 micrograms 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 ED50s of 0.35 and 0.90 micrograms, respectively. Neither IL-4 (1 micrograms, 30 micrograms kg-1, i.v.) nor IL-10 (1 micrograms, 30 micrograms kg-1, i.v.) prevented leucocyte accumulation in the mouse air-pouches when interleukin-8 (IL-8, 1 micrograms) 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 micrograms i.v., 20 min before LPS), but not with IL-10 (1 micrograms 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 microgram 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 microg ml-1, 20 min before LPS), but not with IL-1O (1 microg ml', 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-1beta>) 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.
Perretti
M
M
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St Bartholomew's Hospital, London.
Szabó
C
C
Thiemermann
C
C
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D018845:CD11 Antigens / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D019323:omega-N-Methylarginine
D018845:CD11 Antigens; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016753:Interleukin-10; D015847:Interleukin-4; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase