Concentrations of soluble tumor necrosis factor and interleukin-6 receptors in heatstroke and heatstress

Crit Care Med. 1997 Aug;25(8):1314-9. doi: 10.1097/00003246-199708000-00017.


Objective: Increased proinflammatory cytokine concentrations have been implicated in the pathogenesis of heatstroke. Soluble cytokine receptors can modulate circulating cytokine activities. We examined the possible role of soluble tumor necrosis factor receptors (sTNFR 60, sTNFR 80) and interleukin-6 receptor (sIL-6R) in heatstroke by determining their concentrations before and after cooling, as well as in heatstressed controls.

Design: Prospective controlled study.

Setting: Heatstroke Center, Makkah, Saudi Arabia (1993 pilgrimage).

Patients: Twenty-five consecutive heatstroke patients before and after cooling, 14 heatstressed controls (HSC), and 13 normal controls (NC).

Measurements and main results: Concentrations of sTNFR 60, sTNFR 80, and sIL-6R, as well as their ligands, were measured using commercially available enzyme-linked immunosorbent assay kits. Mean sTNFR 60 concentration was increased in heatstroke (p <.0001, vs. NC; p < .0001, vs. HSC) and in HSC (p = .004, vs. NC). Mean sTNFR 80 concentration was increased in heatstroke and decreased in HSC (p = .01, heatstroke vs. HSC). Mean sIL-6R concentration was decreased in heatstroke and increased in HSC (p = .04, heatstroke vs. NC; p = .001, heatstroke vs. HSC). IL-6 was undetectable in NC and mean IL-6 concentration was more increased in heatstroke than in HSC (p = .001). Rectal temperature and creatinine concentrations correlated significantly with sTNFR 60, sTNFR 80, sIL-6R, and IL-6 concentrations. After cooling, mean concentrations of sIL-6R and sTNFR 80 increased significantly, whereas the mean sTNFR 60 concentration did not change. Residual neurologic deficits were associated with higher precooling IL-6 (p = .002) and postcooling sTNFRs (p < .0001) concentrations.

Conclusions: Significant changes in cytokine receptor concentrations are associated with heatstress. In heatstroke, the changes are more pronounced, and for some cytokine receptors, the changes are in the opposite direction (compared with changes in heatstress). Concentrations of IL-6 and sTNFRs correlate with hyperthermia and outcome. Cooling did not normalize sTNFR concentrations, suggesting failure to control the inflammatory response.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / blood*
  • Case-Control Studies
  • Creatinine / blood
  • Cryotherapy
  • Female
  • Heat Exhaustion / blood
  • Heat Exhaustion / immunology*
  • Heat Exhaustion / therapy
  • Heat Stroke / blood
  • Heat Stroke / immunology*
  • Heat Stroke / therapy
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Interleukin / blood*
  • Receptors, Interleukin-6
  • Receptors, Tumor Necrosis Factor / blood*


  • Antigens, CD
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Creatinine