Mitogenesis in human lymphocytes following brief exposure to hyperthermia

Abstract

Whole blood obtained from normal human donors was incubated in vitro at temperatures ranging from 37°C to 51°C for 30 min. Immedlately following this incubation, whole blood cultures were established for assaying lymphocyte transformation in response to phytohemagglutinin (PHA) pokeweed mitogen (PWM) and concanavalin A (Con A). These cultures were maintained throughout the remainder of the experiment at 37°. Mitogenesis was minimally affected with pretreatment at 41°, significantly impaired at 43°, and totally abolished following brief exposure to temperatures in excess of 44°. In contrast, lymphocyte viability by trypan blue exclusion remained >99 % after a 30 min exposure to temperatures as high as 47° and was approximately 50% after 30 min at 53.5°. The length of exposure time (within the range of 30–120 min) became a critical variable at threshold temperatures at which impairment of mitogenesis was detectable with this assay system. This threshold temperature appears to pie within a very narrow range, similar to that in which tumor cell damage occurs. The necessity for accurate monitoring of both intratumor and core temperatures during treatment is apparent from these data. The response of heat-treated and control lymphocytes to optimal mitogen concentrations was compared to the response to sub-optimal (50% of optimal) concentrations. No differential effects of time (30, 60 min) and temperature (41°, 43°) were evident with the suboptimal concentrations.