Release of an endogenous pyrogen from guinea pig leukocytes: the role of T lymphocytes and correlation with suppression (desensitization) of delayed hypersensitivity.

The pathogenesis of fever in delayed hypersensitivity (DH) was studied in guinea pigs immunized with either ovalbumin or bovine gamma-globulin in complete Freund's adjuvant. In vitro incubation of sensitized lymphocytes with the specific antigen used for immunization resulted in the elaboration of a lymphokine-like factor that activated either monocytes or neutrophils to release endogenous pyrogen (EP), the protein that causes fever. Specifically sensitized T cells appeared to be responsible for release of this EP-inducing factor. Desensitization of the dermal DH response to antigen was produced by several large injections of antigen and was associated with a reduced capacity of lymphocytes from such animals to activate phagocytic cells to release EP. This may explain the reduced fever (pyrogenic tolerance) that occurs when repeated injections of antigen are given to sensitized animals. Fever and the dermal response to DH seem to be closely linked reactions that have evolved to defend the host against invading pathogens. In both reactions, phagocytic cells appear to be activated by lymphokines derived from T lymphocytes specifically responding to microbial antigens.