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

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. Intravenously (i.v.) administered IL‐4 (0.01–10 μg per mouse, approximately 0.3–300 μg kg⁻¹, i.v.) and IL‐10 (0.01‐1 μg per mouse, approximately 0.3–30 μg kg⁻¹, i.v.) dose‐dependently inhibited neutrophil accumulation into a 6‐day‐old murine air‐pouch induced by local application of interleukin‐1β (IL‐1β, 5 ng), with approximate ED₅₀s of 0.35 and 0.90 μg, respectively. Neither IL4 (1 μg, 30 μg kg⁻¹, i.v.) nor IL‐10 (1 μg, 30 μg kg⁻¹, i.v.) prevented leucocyte accumulation in the mouse air‐pouches when interleukin‐8 (IL‐8, 1μg.) 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. 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 IL4 (0.01‐1 μg i.v., 20 min before LPS), but not with IL‐10 (1 μg i.v., 20 min before LPS), caused a dose‐dependent reduction in this LPS‐stimulated formation of nitrite by peritoneal macrophages ex vivo. Activation of murine macrophages with LPS (1 μg 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 IL4 (0.1‐1 μg ml⁻¹, 20 min before LPS), but not with IL‐10 (1 μg ml⁻¹, 20 min before LPS) caused a concentration‐related attenuation of this LPS‐stimulated nitrite formation. Thus, both IL‐4 and IL‐10 inhibit the migration of leucocytes (stimulated by IL‐1β) 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. 1995 British Pharmacological Society