This review focuses on the response of "stress" hormones to heat, exercise (single or repeated bouts), and combinations of these stimuli, with particular reference to their impact upon immune function. Very hot conditions induce a typical stress response, with secretion of catecholamines and cortisol. The catecholamines induce a demargination of leukocytes, and cortisol subsequently causes cells to migrate to lymphoid tissue. Sustained exercise, even in a thermally comfortable environment, induces a larger hormonal response than moderate thermal stress. With moderate exercise, increases in leukocyte numbers are related mainly to plasma norepinephrine concentrations, but with more intense exercise epinephrine concentrations assume a major importance. As exercise continues, plasma cortisol levels also rise, inducing an influx of neutrophils from bone marrow and an efflux of other leukocyte subsets. A combination of exercise and heat stress augments both hormonal and leukocyte responses. But these changes seem to be reversed if temperatures are clamped by exercising in cold water. If a second bout of exercise is performed with an inter-test interval of 30-45 min, neither hormone concentrations nor immune responses show any great cumulative effect under temperate conditions. However, in a hot environment the second exercise bout induces a larger and more persistent neutrophilia. Training influences these various responses mainly by decreasing the stress imposed when exercising at a given absolute work-rate.

This study examined the immunological responses to cold exposure together with the effects of pretreatment with either passive heating or exercise (with and without a thermal clamp). On four separate occasions, seven healthy men [mean age 24.0 +/- 1.9 (SE) yr, peak oxygen consumption = 45.7 +/- 2.0 ml. kg(-1). min(-1)] sat for 2 h in a climatic chamber maintained at 5 degrees C. Before exposure, subjects participated in one of four pretreatment conditions. For the thermoneutral control condition, subjects remained seated for 1 h in a water bath at 35 degrees C. In another pretreatment, subjects were passively heated in a warm (38 degrees C) water bath for 1 h. In two other pretreatments, subjects exercised for 1 h at 55% peak oxygen consumption (once immersed in 18 degrees C water and once in 35 degrees C water). Core temperature rose by 1 degrees C during passive heating and during exercise in 35 degrees C water and remained stable during exercise in 18 degrees C water (thermal clamping). Subsequent cold exposure induced a leukocytosis and granulocytosis, an increase in natural killer cell count and activity, and a rise in circulating levels of interleukin-6. Pretreatment with exercise in 18 degrees C water augmented the leukocyte, granulocyte, and monocyte response. These results indicate that acute cold exposure has immunostimulating effects and that, with thermal clamping, pretreatment with physical exercise can enhance this response. Increases in levels of circulating norepinephrine may account for the changes observed during cold exposure and their modification by changes in initial status.

This study tested the hypothesis that exercise elicits monocytic cytokine expression and that prolonged cold exposure modulates such responses. Nine men (age, 24.6 +/- 3.8 y; VO(2 peak), 56.8 +/- 5.6 ml. kg(-1). min(-1)) completed 7 days of exhausting exercise (aerobic, anaerobic, resistive) and underwent three cold, wet exposures (CW). CW trials comprised

This study investigated the effects of acute ingestion of caffeine (C), ephedrine (E) and their combination (C+E) on time to exhaustion during high-intensity exercise. Using a repeated-measures, double-blind design, eight male subjects exercised on a cycle ergometer at a power output that led to exhaustion after about 12.6 min during a placebo (P) control trial. They did this 1.5 h after ingesting either C (5 mg x kg[-1]), E (1 mg x kg[-1]), C+E, or P. Trials were separated by 1 week. Venous blood was sampled before and during exercise. The mean (SD) times to exhaustion were 12.6 (3.1) (P), 14.4 (4.1) (C), 15.0 (5.7) (E) and 17.5 (5.8) (C+E) min. Only the C+E treatment significantly increased time to exhaustion compared to P. Oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE) and the respiratory exchange ratio (RER) were similar during exercise for all trials. Heart rate during exercise was significantly increased for the C+E and C trials compared to P. Subjective ratings of perceived exertion during exercise were significantly lower after C+E compared to P. All treatments significantly increased lactate levels. Free fatty acid (FFA) levels were significantly increased by C ingestion. Glycerol levels were increased by C+E and C ingestion. Glucose levels were also higher with the drug treatments compared to P. Increased monamine availability after C+E treatment was suggested by measurements of catecholamines and dopamine. In conclusion, the combination of C+E significantly prolonged exercise time to exhaustion compared to P, while neither C nor E treatments alone significantly changed time to exhaustion. The improved performance was attributed to increased central nervous system stimulation.

The contribution of hyperthermia to the differential leukocytosis of exercise remains obscure. This study examined changes in circulating sympathoadrenal hormone concentrations and patterns of leukocyte and lymphocyte subset (CD3(+), CD4(+), CD8(+), CD19(+), CD3(-)16(+)/56(+)) redistribution during exercise, with and without a significant rise of rectal temperature (T(re)). Ten healthy men [age 26.9 +/- 5.7 (SD) yr, body mass 76.0 +/- 10.9 kg, body fat 13.9 +/- 4.6%, peak O(2) consumption: 48.0 +/- 12.4 ml x kg(-1) x min(-1)] exercised for 40 min (65% peak O(2) consumption) during water immersion at 39 or 18 degrees C. T(re) increased from 37.2 to 39.3 degrees C (P < 0.0001) after 40 min of exercise in 39 degrees C water but was held constant to an increment of 0.5 degrees C during exercise in 18 degrees C water. Application of this thermal clamp reduced exercise-associated increments of plasma epinephrine (Epi) and norepinephrine (NE) by >50% (P < 0.05) and abolished the postexercise increase in cortisol. Thermal clamping also reduced the exercise-induced leukocytosis and lymphocytosis. Multiple regression demonstrated that T(re) had no direct association with lymphocyte subset mobilization but was significantly (P < 0.0001) correlated with hormone levels. Epi was an important determinant of total leukocytes, lymphocytes, and CD3(+), CD4(+), CD8(+), and CD3(-)CD16(+)/56(+) subset redistribution. The relationship between NE and lymphocyte subsets was weaker than that with Epi, with the exception of CD3(-)CD16(+)/56(+) counts, which were positively (P < 0.0001) related to NE. Cortisol was negatively associated with leukocytes, CD14(+) monocytes, and CD19(+) B- and CD4(+) T-cell subsets but was positively related to granulocytes. We conclude that hyperthermia mediates exercise-induced immune cell redistribution to the extent that it causes sympathoadrenal activation, with alterations in circulating Epi, NE, and cortisol.