Cytokine changes in patients with heatstroke during pilgrimage to Makkah

Abstract

Circulating levels and role of IL-6, IL-1ra, TNFsr-II and CRP in patients with heatstroke is not fully known. This study correlated levels of these mediators with outcome in 26 patients. In survivors (n=20), IL-6 concentration declined on cooling, whereas in non-survivors levels continued to increase at 6 h following admission before declining. Admission TNFsr-II concentrations in survivors were significantly lower than non-survivors and levels continued to rise in both groups. IL-1ra levels were markedly elevated in both groups. Changes in cytokine levels were not influenced by renal function. Elevated C-reactive protein levels were observed for both groups and remained so despite cooling, furthermore, there was no correlation with alanine aminotransferase levels. The study demonstrated the elevation of the above mediators and suggested a role in the pathogenesis of heatstroke. Markedly elevated levels or those that remained elevated despite cooling were associated with mortality.

Clinical biochemistry of hyperthermia

“…Although IL-6 concentrations at admission were not significantly different between survivors and non-survivors, 36 differences became significant at .6 h following admission. Interestingly, the extent of cytokine response correlated with outcome, where sustained high concentrations despite body cooling were associated with poor outcome.…”

“…IL-6 did not rise significantly until the hyperthermic phase and remained elevated at 24 h of recovery. 42,43 Although it has been shown that high IL-6 levels correlate with heatstroke morbidity and mortality, 36,37 evidence for what would be an expected protective effect of neutralizing IL-6 is not available. Elevated cytokine modulators, i.e.…”

“…45 The temperature associated with heatstroke ranges between 41 and 428C, 40 but temperatures as high as 478C have been reported. 36 Critical thermal maximum, the minimum core-body temperature that is lethal to an organism, is variable, making it difficult to predict thermal injury. Many factors may enhance the risk of heatstroke e.g.…”

“…40 -42 This suggests a protective role for IL-6 which is in contrast to data obtained from correlation studies. 36,38 Furthermore, experimental hyperthermia is characterized by three phases (tri-phasic hyperthermic curve), 41 i.e. (1) An initial rapid increase in core body temperature, followed by (2) an equilibrium plateau, then (3) a rapid increase in core temperature due to breakdown of thermoregulatory mechanisms.…”

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).…”