Cytokine production ex vivo: effect of raised body temperature

This study was designed to examine the effects of hyperthermia in humans on the production of interleukin (IL)-1 alpha, IL-1 beta, tumour necrosis factor (TNF)beta and interferon (IFN)gamma, determined in supernatants from in vitro lipopolysaccharide or phytohemagglutinin stimulated blood mononuclear cells (BMNC), including the effect of indomethacin in the assays on these cytokines. Eight healthy volunteers were immersed into a hot water bath (water temperature 39.5 degrees C) for 2 h, during which their rectal temperature rose to 39.5 degrees C. On a later day they served as their own controls, being immersed into thermoneutral water (34.5 degrees C) for 2 h. Blood samples were collected before, at body temperatures of 38, 39 and 39.5 degrees C, and 2 h after water immersion and at corresponding time points in the control experiment. Hyperthermia did not influence the production of cytokines from stimulated BMNC. Indomethacin in the assays significantly enhanced the ex vivo production of TNF beta at hyperthermic and thermoneutral conditions; this indomethacin enhanced production of TNF beta declined from pre-value in the hyperthermia experiment compared to the control experiment. Furthermore, indomethacin augmented the production of IFN gamma from stimulated BMNC both in the hyperthermic and the control experiments; the indomethacin effect was, however, not different at the two conditions. It is suggested that hyperthermia alters the sensitivity of BMNC to prostaglandins.