Alterations in rat pulmonary macrophage function by the immunosuppressive agents cyclosporine, azathioprine, and prednisolone.
Disturbances of the immune response of the lung induced by the action of immunosuppressive agents on the functional abilities of rat pulmonary alveolar macrophages (PAM) were analyzed following in vitro incubation or in vivo administration (for 30 days) of cyclosporinea, (CsA) azathioprine (Az) or prednisolone (Pr). Two major parameters were analyzed: oxygen consumption and superoxide release as indices of the overall state of oxygen metabolism of these cells reflecting the integrity of PAM oxidative mechanisms of microbicidal activity, and chemotaxis, an event clinically important for normal defense to infection. In vitro incubation with cyclosporine at concentrations as low as 10(-9) M caused a 52% inhibition of PAM superoxide release, but Az had no effect at concentrations up to 10(-6) M. Prednisolone caused a 38% inhibition of superoxide release; comparable levels of inhibition with Pr required concentrations at least 10-fold greater than with cyclosporine. Further experiments indicated that cyclosporine induced a 40% inhibition after contact with PAM for only 30 min. In vivo experiments indicated that cyclosporine (5 mg/kg), Az (20 mg/kg), or Pr (2 or 0.5 mg/kg) administered intraperitoneally had no effect on the number of PAM available for host defense, PAM oxygen consumption, or PAM superoxide release. However, PAM from cyclosporine-treated animals demonstrated complete inhibition of active migration or chemotaxis in modified Boyden chambers upon incubation with formylmethionyl-leucyl-phenylalanine (FMLP). The effect was apparently dampened by simultaneous administration of Pr with cyclosporine. These experiments suggest that with the exception of a marked effect on chemotaxis the in vivo effects of physiologic amounts of cyclosporine on PAM function are modest compared with the marked depression after in vitro addition.
D000818:Animals; D001379:Azathioprine / Q000008:administration & dosage* / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003524:Cyclosporins / Q000008:administration & dosage* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344; D013481:Superoxides / Q000096:biosynthesis
D003524:Cyclosporins; D013481:Superoxides; D011239:Prednisolone; D001379:Azathioprine