EFFECTS OF IN-VITRO HYPERTHERMIA ON PROLIFERATIVE RESPONSES AND LYMPHOCYTE ACTIVITY

Fever is induced by both exogenous products like endotoxin, and endoge nous cytokines, most notably IL-1 and IL-6, and tumour necrosis factor (TNF). These mediators are believed to interact with the hypothalamus , to induce enhanced body temperature. However, little is known about the biological effects of fever on the function of the immune system. We here report that a 90-min pulse of mild hyperthermia (40 degrees C) induces enhanced proliferation of peripheral blood mononuclear cells (PBMC). This proliferative response was completely inhibited by antibo dies to MHC class II, which had no effect on mitogen-induced prolifera tion of PBMC. The enzyme-linked immunospot (ELISPOT) assay is a sensit ive method for detection of single cells secreting antibodies or cytok ines. A 90-min pulse of mild hyperthermia (40 degrees C) induced a sig nificantly enhanced immunoglobulin production in PBMC, as determined b y ELISPOT, indicating B cell activation. The T cell cytokine pattern b oth with and without stimulation with hyperthermia differed between in dividuals. Enhanced interferon-gamma (IFN-gamma) secretion was noted a t 39-41 degrees C. This IFN-gamma response was inhibited by antibodies to MHC class II and thus was MHC class II-restricted and dependent on antigen-presenting cells. None of the individuals tested showed IL-4 response after stimulation with hyperthermia. These findings favour th e notion that fever may play an important role in immune responses, an d it is possible that fever may act as a physiological adjuvant, with effects on the immune system both in infection and inflammation of oth er origins.