Effect of interleukin-4 and interleukin-10 on leucocyte migration and nitric oxide production in the mouse

Br J Pharmacol. 1995 Oct;116(4):2251-7. doi: 10.1111/j.1476-5381.1995.tb15061.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • CD11 Antigens / biosynthesis
  • Chemotaxis, Leukocyte / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-10 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Interleukin-8 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / enzymology
  • Male
  • Mice
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis
  • Up-Regulation / drug effects
  • omega-N-Methylarginine


  • CD11 Antigens
  • Enzyme Inhibitors
  • Interleukin-1
  • Interleukin-8
  • Lipopolysaccharides
  • Interleukin-10
  • Interleukin-4
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase