Changes in concentrations of cytokines in plasma and in hypothalamic push-pull perfusates of guinea pigs were measured within the 1 st hour after intramuscular injections of bacterial Hpopolysaccharide (LPS; Escherichia coli, 20 µg/kg) or solvent (0.9% saline). In control animals injected with solvent, interleukin (IL)-1 and tumor necrosis factor alpha (TNF-α) were not detectable in plasma. Only IL-6 was present in picogram quantities. Within 45 min after injection of LPS, the concentrations of IL-1, TNF-α, and IL-6 increased in the plasma: by several orders of magnitude for TNF-α and about tenfold for IL-G. Picogram amounts of biologically active IL-1 were detected in plasma after injection of LPS. No steady state levels of systemic cytokines were reached during the experimental period. In hypothalamic perfusates of animals injected with the solvent, no IL-1 was detectable. TNF-α could be detected at higher concentrations than IL-6. IL-6 was detectable at tenfold lower concentrations than in the plasma. In animals injected with LPS, the hypothalamic concentration of IL-6 started to increase during the period 15-30 min and the concentrations of TNF-α during the period 30-45 min after LPS injection. The concentrations of IL-6 increased by 300-400% and did not exceed picogram values. No progressive increase of hypothalamic levels of these cytokines was observed during the time course of the experiment. The method used did not detect any changes in the amount of biologically active IL-1 in hypothalamic perfusates of LPS-treated animals. No obvious correlation between concentrations of cytokines in plasma and hypothalamic perfusate was observed, indicating the brain origin of the cytokines. Since the increase in IL-6 goes in parallel with resetting of the body thermostat to the higher level, the data support the hypothesis that the increase in the concentration of IL-6 in the brain, occurring during the early phase of the fever, induces the febrile response.

To differentiate between the effect of cold and hydrostatic pressure on hormone and cardiovascular functions of man, a group of young men was examined during 1-h head-out immersions in water of different temperatures (32 degrees C, 20 degrees C and 14 degrees C). Immersion in water at 32 degrees C did not change rectal temperature and metabolic rate, but lowered heart rate (by 15%) and systolic and diastolic blood pressures (by 11 %, or 12%, respectively), compared to controls at ambient air temperature. Plasma renin activity, plasma cortisol and aldosterone concentrations were also lowered (by 46%, 34%, and 17%, respectively), while diuresis was increased by 107%. Immersion at 20 degrees C induced a similar decrease in plasma renin activity, heart rate and systolic and diastolic blood pressures as immersion at thermoneutrality, in spite of lowered rectal temperature and an increased metabolic rate by 93%. Plasma cortisol concentrations tended to decrease, while plasma aldosterone concentration was unchanged. Diuresis was increased by 89%. No significant differences in changes in diuresis, plasma renin activity and aldosterone concentration compared to subjects immersed to 32 degrees C were observed. Cold water immersion (14 degrees C) lowered rectal temperature and increased metabolic rate (by 350%), heart rate and systolic and diastolic blood pressure (by 5%, 7%, and 8%, respectively). Plasma noradrenaline and dopamine concentrations were increased by 530% and by 250% respectively, while diuresis increased by 163% (more than at 32 degrees C). Plasma aldosterone concentrations increased by 23%. Plasma renin activity was reduced as during immersion in water at the highest temperature. Cortisol concentrations tended to decrease. Plasma adrenaline concentrations remained unchanged. Changes in plasma renin activity were not related to changes in aldosterone concentrations. Immersion in water of different temperatures did not increase blood concentrations of cortisol. There was no correlation between changes in rectal temperature and changes in hormone production. Our data supported the hypothesis that physiological changes induced by water immersion are mediated by humoral control mechanisms, while responses induced by cold are mainly due to increased activity of the sympathetic nervous system.

Over the last 70 years the physiological mechanisms responsible for cold adaptation of humans have been studied intensively in several laboratories. However, in spite of this enormous effort, the principle mechanism of cold adaptation in humans has not yet been sufficiently described. Bittel (1987Bittel ( , 1992, when analysing all the data so far obtained, concluded that a hypothermic-insulative type of adaptation predominates. On the other hand, Young et al. (1986) concluded that cold acclimation in humans appears to be primarily of the insulative type. Our recent work demonstrated the existence of a metabolic type of adaptation due to an increased capacity for adrenaline thermogenesis (Lesn a et al. 1999). This paper attempts to clarify differences in the control of the thermoregulatory responses of non-cold-adapted humans and winter swimmers who are able to withstand very low water temperatures. The significance of observed changes in body temperature control and the activity of heat loss mechanisms in the resistance of humans to cold has been estimated. An attempt is also made to quantify the contribution of catecholamine thermogenesis to the total metabolic response to cold and thus to assess the significance of non-shivering thermogenesis in cold adaptation of humans.

Our study provides evidence of elevated baseline and exercise-induced sympathetic nervous activity and exercise-induced lipolysis in abdominal AT of AN patients.

In the late phase of the fever occurring 120 or more min after i.v. injection of endotoxin (1 microgram/kg) to female rabbits, marked shifts of thresholds for respiratory evaporative heat loss and for peripheral vasodilatation to higher body core temperatures were observed. In contrast, the threshold body core temperature for cold thermogenesis was shifted downwards. As a result, the interthreshold zone was widened. Within the body temperature range of 37.4 to 39.9 degrees C neither heat production or heat loss mechanisms were operant and the body temperature was determined mainly by passive heat transfer between the body and the environment. Outside this zone, the sensitivities of the heat and cold defence activities to changes in body core temperature appeared to be unchanged.

Over the last 70 years the physiological mechanisms responsible for cold adaptation of humans have been studied intensively in several laboratories. However, in spite of this enormous effort, the principle mechanism of cold adaptation in humans has not yet been sufficiently described. Bittel (1987Bittel ( , 1992, when analysing all the data so far obtained, concluded that a hypothermic-insulative type of adaptation predominates. On the other hand, Young et al. (1986) concluded that cold acclimation in humans appears to be primarily of the insulative type. Our recent work demonstrated the existence of a metabolic type of adaptation due to an increased capacity for adrenaline thermogenesis (Lesn a et al. 1999). This paper attempts to clarify differences in the control of the thermoregulatory responses of non-cold-adapted humans and winter swimmers who are able to withstand very low water temperatures. The significance of observed changes in body temperature control and the activity of heat loss mechanisms in the resistance of humans to cold has been estimated. An attempt is also made to quantify the contribution of catecholamine thermogenesis to the total metabolic response to cold and thus to assess the significance of non-shivering thermogenesis in cold adaptation of humans.

Based on observations that fever is suppressed under several physiological circumstances the existence of endogenous antipyretically active molecules has been postulated. A large number of experimental and some clinical studies provided evidence that the neuropeptides arginine vasopressin (AVP), alpha- and gamma-melanocyte stimulating hormones (alpha-MSH, gamma-MSH) and adrenocorticotropic hormone (ACTH) as well as glucocorticoids are capable to antagonize febrile responses to pyrogens. Endogenous antipyresis is mediated by actions of these molecules within the central nervous system or, at least in some cases, by peripheral effects. Brain sites where endogenous antipyresis is activated include the septal area of the limbic system and the anterior hypothalamus. The precise neuronal mechanisms of how the aforementioned endogenous mediators cause a limitation or even suppression of fever are not known. There is, however, evidence that endogenous antipyretics cancel changes in neuronal activities which have been induced by endogenous pyrogens such as cytokines and prostaglandins. At the level of the hypothalamic controller of thermoregulation antipyretic peptides seem to cause a reversion of the pyrogen-induced upward shift of the threshold body core temperature for activation of metabolic heat production. Such a change in thermoregulatory characteristics is compatible with a limitation of fever in strength and duration.

Peptides ghrelin, obestatin and neuropeptide Y (NPY) play an important role in regulation of energy homeostasis, the imbalance of which is associated with eating disorders anorexia (AN) and bulimia nervosa (BN). The changes in ghrelin, obestatin and NPY plasma levels were investigated in AN and BN patients after administration of a high-carbohydrate breakfast (1604 kJ). Eight AN women (aged 25.4±1.9; BMI: 15.8±0.5), thirteen BN women (aged 22.0±1.05; BMI: 20.1±0.41) and eleven healthy women (aged 25.1±1.16; BMI: 20.9±0.40) were recruited for the study. We demonstrated increased fasting ghrelin in AN, but not in BN patients, while fasting obestatin and NPY were increased in both AN and BN patients compared to the controls. Administration of high-carbohydrate breakfast induced a similar relative decrease in ghrelin and obestatin plasma levels in all groups, while NPY remained increased in postprandial period in both patient groups. Ghrelin/obestatin ratio was lower in AN and BN compared to the controls. In conclusions, increased plasma levels of fasting NPY and its unchanged levels after breakfast indicate that NPY is an important marker of eating disorders AN and BN. Different fasting ghrelin and obestatin levels in AN and BN could demonstrate their diverse functions in appetite and eating suppression.