title: Heat stress and/or endotoxin effects on cytokine expression by human whole blood.
abstract: Immune system cytokines induce vascular shock. Tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and bacterial endotoxin (E) circulate in human heatstroke to suggest that E release from a heat-damaged gut may stimulate cytokines that contribute to hypovolemia. However, immune activation by heat-induced tissue necrosis might stimulate cytokine generation in the absence of E. To evaluate this potential and heat stress effects on the anti-inflammatory cytokines, IL-1 receptor antagonist (IL-1ra) and IL-1 soluble receptor II (IL-1srII), a human whole blood (HWB) model was employed in which the presence or absence of E could be controlled. Using thermoelectric technology to regulate the HWB heat exposures, the temperature modulations of lethal heatstroke were precisely replicated (maximum temperature = 42.4 degrees C +/- 0.04 degrees C; thermal area = 52.3 degrees C +/- 1.5 degrees C per min). Cytokine and mRNA measurements employed enzyme-linked immunosorbant-based assay systems. Significant elevations in TNF-alpha, IL-1beta, interleukin 6 (IL-6), and IL-1ra resulted when HWB was exposed to E concentrations (10 ng/ml) reported to circulate in heatstroke. While E-stimulated IL-1ra was significantly decreased by the presence of prior heat stress (PPHS), E-stimulated IL-1beta, TNF-alpha, and IL-6 were not significantly altered by PPHS, but tended to be elevated. IL-1srII expression was unchanged by PPHS and/or E. PPHS in the absence of E did not induce cytokine responses, nor were there elevations in TNF-alpha or IL-1beta mRNA. Thus, some factor normally absent under in vitro conditions, like endotoxin, was required to provoke HWB cytokine expressions and the heat stress and E conditions that characterize heatstroke affected HWB cytokine metabolism to favor a proinflammatory environment.
authors.affiliation: Environmental Pathology/Thermal and Mountain Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts 01760, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: DuBose
authors.forename: James
authors.initials: J
authors.lastname: Balcius
authors.forename: David
authors.initials: D
authors.lastname: Morehouse
mesh_terms: D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000276:immunology; D004926:Escherichia coli; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D017472:Receptors, Interleukin-1 / Q000097:blood; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha