The effect of in vivo hyperthermia on selected lymphokines in man

We have previously demonstrated that artificially induced hyperthermia in man enhances the subsequent production of interferon gamma (IFN-gamma) in isolated leukocyte cultures. The mechanism(s) responsible for this response may involve changes in the circulating lymphocyte populations and may also reflect activation processes occurring in vivo due to hormonal influences. In order to determine whether hyperthermia was associated with other immunostimulatory effects, we measured lymphocyte activation, natural killer cell activity, interleukin-2 (IL-2) production and endotoxin-induced tumor necrosis factor (TNF) activity in blood samples obtained from normothermic (37 degrees C) and hyperthermic (39 degrees C) individuals. Lymphocyte transformation was significantly depressed in post-hyperthermic cultures compared to pre-hyperthermic control cultures. Pre-hyperthermic autologous human plasma was less effective than fetal calf serum in promoting DNA synthesis, while post-hyperthermic plasma suppressed mitogen-induced activation. Natural killer (NK) cell activity was increased by the elevation of core body temperature. Interleukin-2 (IL-2) production in phytohemagglutinin-stimulated mononuclear cell cultures was also elevated when cells were isolated from hyperthermic individuals relative to a paired normothermic control sample. Lipopolysaccharide-induced tumor necrosis factor (TNF) synthesis in monocyte cultures was unchanged by elevation of the core body temperature. This study indicates that in vivo hyperthermia can produce an immunostimulatory effect, an immunosuppressive effect, or no effect on different parameters of the immune system.