Comparative Histologic and Immunologic Studies in Rabbits of Induced Hypersensitivity of the Serum Sickness Type

A histologic and quantitative immunologic study was made on a large group of rabbits injected intravenously with a single dose of crystallized bovine albumin and bled and sacrificed at various intervals after injection. Both cardiovascular and renal lesions were encountered in high incidence. The various stages in the development of these lesions were observed from their first appearance until their complete regression. The cardiac, vascular, and renal alterations were morphologically similar to those of rheumatic fever, polyarteritis nodosa, and acute glomerulonephritis, respectively, in man. In addition to those tissue changes ordinarily attributed to hypersensitivity, peculiar granulomatous lesions consisting of epithelioid and foreign body giant cells were encountered in the follicles of the spleen and in the lymph nodes of a large proportion of the animals receiving the antigen. Similar granulomas in the spleen and lymph nodes as well as in other tissues have been described in polyarteritis nodosa. The present experimental demonstration that an epithelioid and giant cell reaction may result from hypersensitivity provides evidence for the allergic origin of those cases of polyarteritis nodosa of unknown etiology containing this type of lesion. In the present study the time of development of the cardiovascular, renal, and granulomatous lesions was determined in relation to the blood clearance of antigen and the time of appearance of circulating antibody. All the tissue lesions developed during the "immune" phase of antigen elimination and regressed after the antigen had been completely eliminated and free antibody had appeared in the circulation. These temporal relationships indicate that the tissue lesions which occur after the intravenous administration of foreign protein are the result of antigen-antibody combination.