Role of circulating cytokines and chemokines in exertional heatstroke

Abstract

Proinflammatory cytokines IL-1beta, tumor necrosis factor alpha, IL-6; T helper 1 cytokines INF-gamma and IL-2 receptor; and chemokines IL-8, monocyte chemoattractant protein 1, and RANTES are increased in patients with exertional heatstroke. T helper 2 cytokines may play a role as anti-inflammatory cytokines. IL-6, interferon gamma, IL-2 receptor, and monocyte chemoattractant protein 1 may serve as prognostic indicators of disease severity in exertional heatstroke.

The thermoregulatory consequences of heat stroke: Are cytokines involved?

“…T c varies dramatically in heat stroke patients with ranges of 41-42 1C commonly observed, but values as high as $47 1C reported (Bouchama et al, 1993;Chang, 1993;Hammami et al, 1997;Hashim et al, 1997;Lu et al, 2004;Sonna et al, 2004). Austin and Berry (1956) reported T c values ranging from 38.5 1C to 44.0 1C in heat stroke patients, with 10% of the mortalities occurring below 41.1 1C.…”

“…Fever results from the coordinated action of behavioral and physiological mechanisms that increase heat production and decrease heat loss to raise T c to a new elevated level. The presence of tissue injury (Bouchama et al, 2005;Dematte et al, 1988;Lu et al, 2004;Malamud et al, 1946), cytokines (Bouchama et al, 1991(Bouchama et al, , 1993(Bouchama et al, , 2005 and endotoxemia (Graber et al, 1971) in heat stroke suggests that the persistence of fever beyond the initial day of heat exposure (and clinical admission) may be a result of heat-induced SIRS. This long-term occurrence of fever may also account for it not being widely recognized as a heat stroke recovery response in animal studies.…”

Increased cytokine and chemokine gene expression in the CNS of mice during heat stroke recovery

“…For example, HS patients and animal models often display core temperature (T c ) disturbances (e.g., hypothermia, fever) during recovery that occur in the absence of damage to the preoptic anterior hypothalamus (POAH), which is considered the main thermoregulatory center in the brain (1,21,25). Since many of the thermoregulatory and sickness symptoms of HS are transient in nature, they are likely due to inflammatory changes rather than heat cytotoxicity and brain damage per se.The central and systemic mechanisms mediating the SIRS to HS have not been fully elucidated, but circulating cytokines [e.g., interleukin (IL)-1␤, IL-6, tumor necrosis factor (TNF)-␣] and chemokines [monocyte chemoattractant protein-1 (MCP-1)] have been implicated in the morbidity of this syndrome (6,19,23). High circulating IL-6 showed the highest correlation with neurological symptoms and morbidity of HS patients and animal models (4,6,19).…”

“…The central and systemic mechanisms mediating the SIRS to HS have not been fully elucidated, but circulating cytokines [e.g., interleukin (IL)-1␤, IL-6, tumor necrosis factor (TNF)-␣] and chemokines [monocyte chemoattractant protein-1 (MCP-1)] have been implicated in the morbidity of this syndrome (6,19,23). High circulating IL-6 showed the highest correlation with neurological symptoms and morbidity of HS patients and animal models (4,6,19).…”

Thermoregulatory responses to environmental toxicants: The interaction of thermal stress and toxicant exposure

“…During prolonged heat exposure, autonomic mechanisms of thermoregulatory control, such as sweating may become exhausted, resulting in dramatic increases in T c with values as high as ∼47°C reported in patients (Bouchama et al, 1991;1993;Chang, 1993;Hammami et al, 1997;Hashim et al, 1997;Lu et al, 2004;Sonna et al, 2004). Hypothermia (∼ 7°C below baseline) and fever (∼ 1-2°C above baseline) are long-term heat stroke recovery responses that are less well-recognized, but are thought to be a consequence of the systemic inflammatory response (SIRS) that occurs in response to endotoxin leakage from the ischemic GI tract (Attia et al, 1983;Austin and Berry, 1956;Leon et al, 2005;Malamud et al, 1946;Romanovsky and Blatteis, 1996;Wilkinson et al, 1988;Wright, 1976).…”