Experimental Glomerulonephritis. IX. Factors Influencing the Development of Kidney in Adjuvant Nephritis in Rats.

Abstract

Summary An investigation was made into the importance of the immunization, strain of host rat, and antigen in the induction of kidney in adjuvant nephritis. It was found that variations in each of these 3 elements could significantly alter the development and course of the disease. Nephritogenic streptococci were ineffective substitutes for mycobacterium in the adjuvant. However, replacement of the usual emulsifying agent in the adjuvant, Arlacel C, with a more phlogogenic agent, Arlacel A, led to increased severity of disease. The strain of rat used was also important: inbred Lewis rats were most susceptible, inbred Fisher rats were next, outbred Sprague-Dawley rats were next and inbred Buffalo rats were refractory to development of nephritis. Several observations relating to the effectiveness of antigen were made. First, the most potent source of antigen appeared to be Sprague-Dawley kidneys. Second, isologous kidneys and heterologous kidneys provided less effective antigens than homologous kidneys. Third, it appeared that kidney antigen, in addition to stimulating an antibody response, had to be present in considerable quantity to induce a lasting renal injury. Fourth, multiple injections of kidney in adjuvant produced a more severe nephropathy than a single injection containing a comparable amount of kidney protein. This was possibly a manifestation of the increased nephrotoxic action of Freund's adjuvant in the former situation. Fifth, it was found that injections could be given at weekly instead of bimonthly intervals, thereby shortening the induction period of the disease by several weeks. Sixth, when a native kidney preparation was chemically altered by coupling it to diazonium derivatives of arsanilic and sulfanilic acid, and then used to immunize rats, a more severe disease was produced.