This study examined endotoxin-mediated cytokinemia during exertional heat stress (EHS). Subjects were divided into trained [TR; n=12, peak aerobic power (VO2peak)=70+/-2 ml.kg lean body mass(-1).min(-1)] and untrained (UT; n=11, VO2peak=50+/-1 ml.kg lean body mass(-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 endotoxin, lipopolysaccharide binding protein, circulating cytokines, and intranuclear NF-kappaB translocation. Baseline and Exh samples were also stimulated with LPS (100 ng/ml) and cultured in vitro in a 37 degrees C water bath for 30 min. Phenotypic determination of natural killer cell frequency was also determined. Enhanced blood (104+/-6 vs. 84+/-3 ml/kg) and plasma volumes (64+/-4 vs. 51+/-2 ml/kg) were observed in TR compared with UT subjects. EHS produced an increased concentration of circulating endotoxin in both TR (8+/-2 pg/ml) and UT subjects (15+/-3 pg/ml) (range: not detected to 32 pg/ml), corresponding with NF-kappaB translocation and cytokine increases in both groups. In addition, circulating levels of tumor necrosis factor-alpha and IL-6 were also elevated combined with concomitant increases in IL-1 receptor antagonist in both groups and IL-10 in TR subjects only. Findings suggest that the threshold for endotoxin leakage and inflammatory activation during EHS occurs at a lower temperature in UT compared with TR subjects and support the endotoxin translocation hypothesis of exertional heat stroke, linking endotoxin tolerance and heat tolerance.

Older adults typically experience greater levels of thermal strain during physical efforts in the heat compared to young individuals. While this may be related to an age-dependent reduction in whole-body sweating, no study has clearly delineated at what age this occurs. In the present study, we report direct measurements of human heat dissipation during physical activity in the heat in males ranging in age from 20–70 years. Eighty-five males performed four 15-min bouts of cycling separated by 15-min rest periods, in a calorimeter regulated to 35°C and 20% relative humidity. Direct calorimetry was used to measure total heat loss (whole-body evaporative heat loss and dry heat exchange). We also used indirect calorimetry as a continuous measure of metabolic heat production. Body heat storage was calculated as the temporal summation of heat production and total heat loss over the experimental session. Whole-body sweat rate (WBSR) was calculated from measurements of evaporative heat loss. Males were divided into five age categories for the analysis of WBSR and body heat storage: 20–31 years (n = 18), 40–44 years (n = 15), 45–49 years (n = 15), 50–55 years (n = 21) and 56–70 years (n = 16). Relative to young males, WBSR was reduced in males aged 56–70 during each exercise (all P<0.05), in males aged 50–55 during the second (P = 0.031) and third exercises (P = 0.028) and in males aged 45–49 during the final exercise bout (P = 0.046). Although not significantly different, 40–44 years old males also had a lower rate of heat loss compared to younger males. Over the sum of two hours, the change in body heat content was greater in males 40–70 years compared to young males (all P<0.05). Our findings suggest that middle-aged and older adults have impairments in heat dissipation when doing physical activity in the heat, thus possibly increasing their risk of heat-related illness under such conditions.

Hardcastle S, Kenny GP. Whole body heat loss is reduced in older males during short bouts of intermittent exercise. Am J Physiol Regul Integr Comp Physiol 305: R619 -R629, 2013. First published July 24, 2013 doi:10.1152/ajpregu.00157.2013.-Studies in young adults show that a greater proportion of heat is gained shortly following the start of exercise and that temporal changes in whole body heat loss during intermittent exercise have a pronounced effect on body heat storage. The consequences of short-duration intermittent exercise on heat storage with aging are unclear. We compared evaporative heat loss (HE) and changes in body heat content (⌬Hb) between young (20 -30 yr), middle-aged (40 -45 yr), and older males (60 -70 yr) of similar body mass and surface area, during successive exercise (4 ϫ 15 min) and recovery periods (4 ϫ 15 min) at a fixed rate of heat production (400 W) and under fixed environmental conditions (35°C/20% relative humidity). HE was lower in older males vs. young males during each exercise (Ex1: 283 Ϯ 10 vs. 332 Ϯ 11 kJ, Ex2: 334 Ϯ 10 vs. 379 Ϯ 5 kJ, Ex3: 347 Ϯ 11 vs. 392 Ϯ 5 kJ, and Ex4: 347 Ϯ 10 vs. 387 Ϯ 5 kJ, all P Ͻ 0.02), whereas HE in middle-aged males was intermediate to that measured in young and older adults (Ex1: 314 Ϯ 13, Ex2: 355 Ϯ 13, Ex3: 371 Ϯ 13, and Ex4: 365 Ϯ 8 kJ). HE was not significantly different between groups during the recovery periods. The net effect over 2 h was a greater ⌬Hb in older (267 Ϯ 33 kJ; P ϭ 0.016) and middle-aged adults (245 Ϯ 16 kJ; P ϭ 0.073) relative to younger counterparts (164 Ϯ 20 kJ). As a result of a reduced capacity to dissipate heat during exercise, which was not compensated by a sufficiently greater rate of heat loss during recovery, both older and middle-aged males had a progressively greater rate of heat storage compared with young males over 2 h of intermittent exercise. evaporative heat loss; aging; calorimetry; thermal transients A NUMBER OF STUDIES HAVE EXAMINED age-related differences in thermoregulatory control during prolonged exercise (range 30 -90 min) in the heat [range: 30 -49°C/20 -60% relative humidity (RH)] (4, 11-13, 20, 23, 26, 29, 33, 34). Some studies reported no differences in thermoregulatory function (4,20,23,29,33), whereas others found significant age-related impairments in heat loss capacity (e.g., reduced local sweating rate/onset/sensitivity and/or greater increments in core and skin temperatures) (11-13, 26, 34). It is possible that these discrepancies reflect that in some studies, older adults were able to achieve heat balance, while in other studies, heat load exceeded their physiological maximal sweating capacity; hence, differences in local sweat rate and/or core temperature were evident. What these studies did not examine, however, is whether age-related impairments in heat loss capacity occur during exercise of short duration (i.e., 15 min) when the rate of heat storage has been shown to be the greatest (21).At the onset of exercise, the rate of metabolic heat production increases immediately and is not i...

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 ϩ monocyte subsets during exertional heat stress (EHS). Subjects were divided into endurance-trained [TR; n ϭ 12, peak aerobic power (V O2peak) ϭ 70 Ϯ 2 ml⅐ kg lean body mass (LBM) Ϫ1 ⅐ min Ϫ1 ] and sedentary-untrained (UT; n ϭ 11, V O2peak ϭ 50 Ϯ 1 ml⅐ kg LBM Ϫ1 ⅐ min Ϫ1 ) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber (40°C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5°C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0°C/Exh) were analyzed for cytokines (TNF-␣, IL-1␤, IL-6, IL-1ra, and IL-10) in CD14 ϩϩ CD16 Ϫ /CD14 ϩ CD16 ϩ 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 g/ml) or heat shocked (42°C) and cultured in vitro for 2 h. A greater temperature-dependent increase in CD14 ϩ CD16 ϩ cells was observed in TR compared with UT subjects as well as a greater LPS tolerance following in vitro LPS stimulation. TNF-␣ and IL-1␤ cytokine expression was elevated in CD14 ϩ CD16 ϩ but not in CD14 ϩϩ CD16 Ϫ 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 ϩ subsets. Findings suggest that circulating CD14 ϩ CD16 ϩ , but not CD14 ϩϩ CD16 Ϫ 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. immune function; cardiovascular/thermoregulatory strain; flow cytometry; heat shock protein PERIPHERAL BLOOD MONOCYTES play an important role in protection against invading pathogens and activation of innate immunity (46). Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82, 90). The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6, 62, 64, 90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the clas...

These findings suggest that older females have a lower capacity for whole-body EHL compared with younger females during short intermittent exercise in the heat performed at a fixed rate of metabolic heat production.