Differential effects of in vitro and in vivo hyperthermia on the production of interleukin-10

Objective: To determine whether hyperthermia activates an anti-inflammatory response. Design: A prospective study. Setting: Heatstroke Center, Makkah, and King Faisal Specialist Hospital, Riyadh, Saudi Arabia. Patients: Twenty-five heatstroke patients pre-cooling (rectal temperature 42.4±0.8 °C) (group 1) and 13 normothermic heat-stressed subjects were studied (group 2). Twelve of the 25 heatstroke patients were also studied post-cooling (group 3). Mononuclear cells from six healthy blood donors resting at 24 °C were used for in vitro study. Interventions: Mononuclear cells were cultured at a concentration of 1×106/ml without and with lipopolysaccharide (LPS) added at concentration of 10, 100, and 1000 ng/ml. The cells were incubated for 24 h at 37, 39, 41, and 43 °C. ELISA was used to measure IL-10 in the supernatant and plasma from heatstroke and heat-stressed subjects. Results: All patients in group 1, 40% of group 2, and 37% of group 3, showed elevation of IL-10 (1289±2519, 248±393, and 172±226 pg/ml, respectively) compared with normal control levels, (<100 pg/ml) P<0.05. IL-10 level on admission did not correlate with degree of hyperthermia. During 24 h incubation at 37 °C without LPS, no IL-10 was detected, whereas with 10 ng/ml LPS, monocytes released 658±291 pg IL-10/106 cells. At 39 °C and 41 °C IL-10 release was decreased to 225±114, and 245±90 pg/106 cells, respectively; and was completely inhibited at 43 °C (67±10 pg/106 cells), P<0.0001. Conclusion: Heat-stress with and without hyperthermia is associated with anti-inflammatory response in vivo. However, it does not seem to be the direct effect of heat on monocytes, suggesting that other environmental or genetic factors may be involved.