Thermal homeostasis in systemic inflammation: modulation of neuronal mechanisms.

Fever can be defined as a specific model of body temperature control, modified by action of humoral substances released due to bacterial infection. Under laboratory conditions exogenous and endogenous pyrogens affect nervous endings in the body periphery, as well as thermosensitive neurons in the hypothalamus, which first manifests as a shock reaction and then as shifts of temperature thresholds for activation of thermoregulatory effectors (cold thermogenesis, vasomotion, sweating or panting) to higher body temperatures. During the later phase of fever, the temperature threshold for cold thermogenesis starts to move downwards, while the thresholds for other thermoregulatory outputs remain elevated, the result being enlarging of the interthreshold zone. This creates conditions for cooling of the body and for termination of the fever. During different phases of fever cytokines, prostaglandins, neuropeptides and catecholamines participate in modulation of mechanisms regulating thermoregulatory functions. This paper aims to specify the role of individual cytokines in induction of fever, as well as in activation of thermoregulatory centers as well as individual thermoregulatory effectors and to define differences in their mode of action. The paper further attempts to summarize our knowledge on humoral modulation of the cytokine release. It is concluded that cytokines are not the primary factors responsible for setting of the body thermostat during fever.