Macrolide antibiotics protect against immune complex-induced lung injury in rats: role of nitric oxide from alveolar macrophages.
Macrolide antibiotics have unique immunomodulatory actions apart from antimicrobial properties. We studied the effects of macrolides on IgG immune complex (IgG-ICx)-induced lung injury in rats in vivo and in vitro. Intrapulmonary deposition of IgG-ICx produced a time-dependent increase in the concentration of NO in exhaled air. There were corresponding increases in the number of neutrophils accumulated into alveolar spaces, and lung wet-to-dry weight ratio. All of these changes were inhibited by pretreatment with erythromycin or josamycin, but not by amoxicillin or cephaclor. Incubation of cultured pulmonary alveolar macrophages caused up-regulation of NO production and expression of inducible NO synthase mRNA, an effect that was dose dependently inhibited by erythromycin, roxithromycin, or josamycin. The macrolides also reduced IgG-ICx-induced release of IL-1beta and TNF-alpha, but did not alter the release of NO induced by exogenously added IL-1beta and TNF-alpha. These results suggest that macrolide antibiotics specifically inhibit immune complex-induced lung injury presumably by inhibiting cytokine release and the resultant down-regulation of inducible NO synthase gene expression and NO production by rat pulmonary alveolar macrophages.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical University School of Medicine, Japan. jtamaoki@xc4.so-net.ne.jp
Kondo
M
M
Kohri
K
K
Aoshiba
K
K
Tagaya
E
E
Nagai
A
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000633:toxicity*; D001944:Breath Tests; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004917:Erythromycin / Q000097:blood / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D000936:Antigen-Antibody Complex; D016207:Cytokines; D009569:Nitric Oxide; D004917:Erythromycin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat