Control of glucan-induced systemic granulomatosis by cyclosporine A.
This study has shown that cyclosporine A (CyA), under certain conditions, is a powerful inhibitor of intravascular and extravascular monocyte/macrophage accumulation. Experiments were carried out in Lewis rats in which intravenous injection of particulate glucan calls forth a striking granulomatous response in lung, liver, and spleen and produces a marked stimulation of splenic erythro- and myelopoiesis. In agreement with the results of others, there was also a considerable elevation in monocyte/macrophage chemoattractant levels in the bronchoalveolar lavage fluid, which is held to be a key reaction in the pathogenesis of the histologic lesions. Treatment of the animals with subcutaneous injections of CyA prevented the rise in the chemoattractant activity and suppressed the granulomatous organ infiltration as well as the splenic hemopoiesis. The findings supply new insights into the activities of CyA and would support its clinical use in macrophage-dominated diseases.
Geratz
J D
JD
Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599, USA.
Pryzwansky
K B
KB
Anderle
S K
SK
Tidwell
R R
RR
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D002633:Chemotaxis; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005936:Glucans / Q000633:toxicity*; D015745:Granuloma, Foreign-Body / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013158:Splenic Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D005936:Glucans; D016572:Cyclosporine