There are increasing clinical (1-6), functional (7), radiological (4,5,6,8), and histological (3,(9)(10)(11)(12)(13)(14) evidences that interstitial pneumonitis with or without pulmonary fibrosis may develop in patients with underlying diseases which appear to be associated with circulating antigen-antibody complexes. The pathogenesis of these human lesions, however, has not been studied in experimental animal models. Rabbits with acute or chronic serum sickness have not shown pulmonary changes (15, 16). On the other hand, acute anaphylactic shock, a condition characterized by preferential precipitation of circulating antigen-antibody complexes within the lumina of pulmonary capillaries (17)(18)(19), is caused by a mechanism which has no relationship with chronic pulmonary diseases in man.These considerations have suggested the possibility that antigen-antibody complexes present in large amount and for prolonged periods of time in the circulation of rabbits may localize in their lungs, thereby producing inflammatory reactions comparable to those commonly seen in the kidneys of the same animals.The results of the studies described here show that rabbits making a hyperactive antibody response to injections of bovine serum albumin (BSA), 1 when maintained in a state of relative antigen-antibody equivalence by high, multiple, daily doses of BSA, develop membranous and/or proliferative lesions of the lung which are associated with deposition of antigen, host immunoglobulin, complement, and fibrinogen in pulmonary structures. The inflammatory changes, which are presumably produced by antigen-antibody complexes, cover the morphologic spectrum of certain human interstitial pneumonitis (20, 21). Materials and MethodsInduction of Serum Sickness.--58 female albino rabbits weighing 2-3 kg were purchased from a local breeder, and fed Purina rabbit pellets and water ad libitum. 51 rabbits were used

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The mechanisms that allow circulating basement membrane antibodies (Ab) to interact with the alveolar basement membrane (ABM) inducing Goodpasture's hemorrhagic pneumonitis are unknown. In laboratory animals the ABM is inaccessible to phlogogenic amounts of ABM Ab unless the permeability of the unfenestrated alveolar endothelium is increased. This study was designed to test the hypothesis that in the mouse polypeptide mediators, generated by activated lymphoid cells or cells infected by viruses, contribute to the pathogenesis of passive Goodpasture's hemorrhagic pneumonitis. In naive mice that received rabbit ABM Ab, these bound to the glomerular basement membrane but not to the ABM and their lungs were normal. In the lungs of mice injected with human recombinant IL-2 and IFN-a specific binding of ABM IgG, C3, and fibrinogen to the ABM, diffuse and severe erythrocyte extravasation, and accumulation of mononuclear and polymorphonuclear leukocytes were constantly observed. ABM Ab and IL-2 or ABM Ab and IFN-a did not produce comparable effects. Mice injected only with IL-2 and IFN-a had enlarged, edematous lungs without pulmonary hemorrhages. The results show that the synergism of IL-2 and IFN-a convert the lung into a preferential target for AMB Ab, suggesting that cytokines may have a role in the pathogenesis of human Goodpasture's pneumonitis. (J. Clin. Invest. 1990Invest. . 85:1507Invest. -1515 Goodpasture's pneumonitis * basement membrane antibodies.

The possible role of circulating immune complexes (IC) in the production gastrointestinal lesions was studied in rabbits with chronic serum sickness (CSS) induced by multiple daily injections of bovine serum albumin (BSA). All rabbits generating a marked antibody response developed IC glomerulonephritis. In approximately 50% of these rabbits granular deposits of BSA, rabbit IgG, and C3 were also found in the gastrointestinal tract. The immune deposits in the gastrointestinal tract were mainly present in the vessel walls, close to the intestinal glands and the surface epithelium, and between the smooth muscle cells. This was accompanied by slight to moderate edema of the mucosa and the submucosa and mild infiltration of inflammatory cells. Electron-densedeposits were found in a pattern corresponding to that observed for BSA, rabbit IgG, and C3. Degranulated neutrophils, basophils, and mast cells were noticed in the interstitium. The presence in the same areas of granular deposits of BSA, IgG, and C3, corresponding to electron-dense deposits, suggests that the deposits contain BSA-anti-BSA complexes. These findings show that in rabbits with CSS circulating IC may localize and induce injury in the gastrointestinal tract.