Studies on antimacrophage globulin

Abstract

The immunosuppressive and anti-inflammatory properties of rabbit antirat macrophage (AMG) and rabbit antirat thymocyte globulin (ALG) have been compared. In vitro experiments showed that both AMG and ALG contained antibodies directed against rat thymocytes and macrophages. When AMG was absorbed with large numbers of thymocytes, the final product was found to lack agglutinating and cytotoxic antibodies against such cells. However, AMG was cytotoxic to rat peritoneal macrophages at a dilution of 1/512 while the ALG cytotoxic titre was 1/64. It was also shown that AMG was able to suppress phagocytosis by peritoneal mononuclear cells while ALG was ineffective.

The immunosuppressive activity of AMG and ALG when given at the time of induction of the immune response was studied in vivo. Rats were pretreated with the antisera prior to induction of Freund's adjuvant arthritis and immunization with sheep erythrocytes. Administration of ALG prior to induction of adjuvant arthritis resulted in complete inhibition of the disease while AMG treated rats developed arthritis. ALG treated rats produced almost no haemagglutinating antibody to sheep erythrocytes used as antigen while the AMG treated group developed titres not significantly different from the control group. When the same animals were rechallenged with sheep erythrocytes 5 weeks later the response of the AMG treated group was similar to that of controls, while the ALG treated animals developed a primary antibody response.

When the antisera were given to animals coinciding with the development of generalized arthritis in order to study their anti-inflammatory activity, AMG treated rats showed a small decrease in the severity of arthritis. ALG was much more effective in reducing the inflammatory signs of the disease and its suppressive effects lasted for 2 weeks after the last injection. The anti-inflammatory properties of ALG were also evident in the marked inhibition of the granuloma in the adjuvant-injected paw which paralleled the effects of treatment on the polyarthritis. Similarly, ALG treatment produced a severe depression of the delayed hypersensitivity response to tuberculin while AMG was ineffective.

The above results indicate that ALG is a strong anti-inflammatory and immunosuppressive agent while AMG has no immunosuppressive properties and is only a mild anti-inflammatory agent.