Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Selkirk GA, McLellan TM, Wright HE, Rhind SG. Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals. Am J Physiol Regul Integr Comp Physiol 296: R575-R586, 2009. First published January 21, 2009; doi: 10.1152/ajpregu.90683.2008.-This study examined intracellular cytokine, heat shock protein (HSP) 72, and cellular apoptosis in classic and inflammatory CD14(+) monocyte subsets during exertional heat stress (EHS). Subjects were divided into endurance-trained [TR; n = 12, peak aerobic power ( V-O2peak) = 70 +/- 2 ml (.) kg lean body mass (LBM) (-1) (.) min(-1)] and sedentary-untrained (UT; n = 11, V-O2peak = 50 +/- 1 ml (.) kg LBM-1 (.) min(-1)) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber ( 40 degrees C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5 degrees C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0 degrees C/ Exh) were analyzed for cytokines ( TNF-alpha, IL-1 beta, IL-6, IL-1ra, and IL-10) in CD14(++) CD16(-)/CD14(+)CD16(+) and HSP72/apoptosis in CD14(Bri)/CD14(Dim) subsets. In addition, serum levels of extracellular (e) HSP72 were also examined. Baseline and Exh samples were separately stimulated with LPS ( 1 mu g/ml) or heat shocked ( 42 degrees C) and cultured in vitro for 2 h. A greater temperature-dependent increase in CD14(+)CD16(+) cells was observed in TR compared with UT subjects as well as a greater LPS tolerance following in vitro LPS stimulation. TNF-alpha and IL-1 beta cytokine expression was elevated in CD14(+) CD16(+) but not in CD14(++) CD16(-) cells. A greater induction of intracellular HSP72 and eHSP72 was observed in TR compared with UT subjects, which coincided with reduced apoptosis at Exh and following in vitro heat shock. Induced HSP in vitro was not uniform across CD14(+) subsets. Findings suggest that circulating CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, contribute to the proinflammatory cytokine profiles observed during EHS. In addition, the enhanced HSP72 response in endurance-trained individuals may confer improved heat tolerance through both anti-inflammatory and anti-apoptotic mechanisms.