Suppression of rat adjuvant disease by cyclophosphamide pretreatment: evidence for an antibody mediated component in the pathogenesis of the disease.
Cyclophosphamide (Cy), given intraperitoneally at a dose of 100 mg per kg body weight 3 days before adjuvant, was found to abolish the development of adjuvant disease in the PVG/c rat. This treatment, however, enhanced the delayed hypersensitivity responses to purified protein derivative of tuberculin (PPD) developed by these animals. Lower doses of Cy caused a partial inhibition of arthritis which was dose-related. When the time between giving Cy and the injection of adjuvant was increased, a gradual time-dependent recovery of the response was observed. The arthritic response was restored by the passive transfer of 7.6 x 10(7) to 1.5 x 10(8) normal syngeneic spleen cells, although the development of secondary lesions was delayed by 7-14 days. The response could also be restored by the transfer of small amounts of serum from arthritic, but not normal, rats. Large amounts of serum failed to restore the response. Additional evidence that pretreatment with Cy preferentially depleted the B lymphocytes was obtained by the histological examination of the lymphoid tissue. It was also shown that the primary antibody response to sheep erythrocytes was abolished by Cy, but that skin allograft rejection was unaffected. A partial inhibition of the acute inflammatory reaction to carrageenan was observed 3 days after giving Cy. It is suggested that the pathogenesis of adjuvant arthritis involves an immune complex-mediated phase, whihc initiates the joint lesions. Once these lesions have formed, cell-mediated immune mechanisms predominate in the development of the disease. It is not known whether the persistence of immune complexes is necessary to maintain the lesions.
D000818:Animals; D000906:Antibodies; D000917:Antibody Formation; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control; D001402:B-Lymphocytes / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006968:Hypersensitivity, Delayed; D007116:Immunization, Passive; D008297:Male; D051381:Rats; D013997:Time Factors
D000906:Antibodies; D003520:Cyclophosphamide