Amiodarone pulmonary toxicity in the rat is associated with increased lavage immunoglobulin and alveolar macrophages primed for increased interleukin-1 secretion.
To determine whether a hypersensitivity reaction played a role in amiodarone-induced pulmonary inflammation and affected humoral immunity, we examined pulmonary immunoglobulin (Ig) levels, alveolar macrophage release of interleukin-1 (IL-1)-like activity, and the ability to generate both systemic and pulmonary humoral immune responses after immunization. Levels of IgG, IgM, and albumin in lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA) in control rats and rats fed drug for 3, 8, 11, and 30 wk. Control rats showed no change in lavage Ig levels at any time point. However, drug-fed rats had a significant increase in IgG/albumin at 11 and 30 wk and IgM/albumin at 30 wk. To determine whether alveolar macrophages were in an activated state, the amount of IL-1-like activity released by cells from control rats was compared with drug-fed rats, using the standard C3H/HeJ thymocyte proliferation assay. We found no difference in the spontaneous release of IL-1 activity, but lipopolysaccharide-stimulated macrophages from the drug-fed rats produced significantly more IL-1 than did control macrophages. Finally, to examine antibody responses, control and drug-fed rats were immunized and boosted with 1 mg/ml of ovalbumin (OA) in adjuvant followed by an intratracheal immunization of OA. There was no difference in antibody titers measured by ELISA. In conclusion, although there is some suggestion of an immune-mediated component in amiodarone-induced pulmonary inflammation, the increase in lymphocytes and lavage Ig appears too late to be the sole cause.
Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141.
B D
BD
Wilson
M L
ML
Lippmann
D000638:Amiodarone / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D004342:Drug Hypersensitivity; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007375:Interleukin-1 / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007375:Interleukin-1; D000638:Amiodarone