The administration of large amounts of vitamin A to rabbits has been shown to result in depletion of cartilage matrix. The normal basophilic, metachromatic, and Alcian blue staining properties of the matrix are lost, especially in articular and epiphyseal cartilage. The cartilage cells remain intact, but are reduced in size. These changes sometimes appeared as early as 48 hours after the initiation of daily injection of 1 million units of vitamin A, and were usually well established by 5 days. Some rabbits failed to show changes in cartilage, even after 5 daily injections. Increased amounts of material presumed to be chondroitin sulfate were present in the sera of vitamin A-treated rabbits, usually by 72 hours after the first injection. This was demonstrated by a turbidimetric procedure using hexamminecobaltic chloride. In rabbits given sulfur-35 (Na2S35O4) 5 days before the initiation of vitamin A treatment, it was shown that sulfur-35 was lost from articular and epiphyseal cartilage. This was associated with an increase in the non-dialyzable sulfur-35 in both serum and in the cobalt-precipitable material. These rabbits also excreted more sulfur-35 than rabbits not given vitamin A. There was a reduction in sulfur-35 activity in chondromucoprotein extracted from the ear cartilage of vitamin A-treated rabbits. The changes are interpreted as indicating that the administration of large amounts of vitamin A to rabbits results in removal of chondroitin sulfate from cartilage matrix. The administration of small amounts of crude papain causes histologic changes in cartilage that are remarkably similar to those seen in vitamin A-treated rabbits. The possibility is suggested that the changes in cartilage produced by administration of vitamin A to rabbits may be the result of activation of a proteolytic enzyme or enzymes, with properties similar to those of papain.

The pathogenesis of experimental serum sickness in the rabbit has been extensively investigated since the description of the characteristic lesions, glomerulonephritis, arteritis, and endocarditis, by Rich and Gregory (1). It has been established by several investigators that the lesions appear during the immune phase of antigen elimination from the blood, at a time when antigen-antibody complexes are present in the circulation (2, 3). The disease is of short duration and the lesions regress after antigen has been completely eliminated and free antibody appears in the blood (2). Dixon and coworkers demonstrated antigen and probably antibody in the lesions of serum sickness by means of the fluorescent antibody technique (3), thus supporting Germuth's hypothesis (2) that the pathological changes are the result of localization of antigenantibody complexes as such at the sites where the lesions appear. The validity of this interpretation has been strengthened by observations on the biological properties of antigen-antibody complexes. The important role of these complexes in the pathogenesis of certain hypersensitivity states has only recently been recognized. It has been shown that they can produce anaphylaxis in guinea pigs (4) and mice (5, 6), contraction of isolated guinea pig smooth muscle (7) and inflammatory changes in the skin (8), whose severity is proportional to the amount injected.More direct evidence for the role of soluble antigen-antibody complexes in the pathogenesis of serum sickness was provided by observations previously reported from this laboratory showing that the intravenous injection of large amounts of soluble antlgen-antibody complexes produced the characteristic lesions of serum sickness in normal mice within 36 hours (6, 9).In the present study these observations have been extended. The incidence of the various lesions has been studied with several antigen-antibody systems. The evolution and duration of the lesions, the possible role of anaphylaxis in their pathogenesis, the effect of cortisone, and of an antihistamine have also been investigated. The extent to which the complexes used were dissociated in vivo was explored.

The intravenous administration to rats of soluble antigen-antibody complexes in antigen excess resulted in acute glomerulonephritis. This occurred with both rabbit antiovalbumin and rabbit anti-BSA systems. The rats so treated regularly showed proteinuria and elevation of blood urea nitrogen. These findings are compared with those reported in rats injected with anti-kidney serum.