The effect of heat on cytokine production in rat endotoxemia.
OBJECTIVE
To determine whether heat stress protects the endotoxemic rat by up-regulation of the counterinflammatory cytokine interleukin (IL)-10, thereby attenuating the inflammatory response.


METHODS
A total of 16 rats were assigned to either the heat stress group (n = 8) or the control group (n = 8). The heat stress group was warmed to a temperature of >42 degrees C (107.6 degrees F) rectally for 10-15 mins; 20 hrs later, all rats were intubated, paralyzed, and ventilated. After jugular venous and arterial catheterization, endotoxin was given intravenously. Arterial blood was removed at 0, 2, 4, and 5 hrs for blood gases, tumor necrosis factor (TNF)-alpha, nitric oxide metabolites (NO), IL-10, and macrophage inflammatory protein (MIP)-2. The alveolar macrophages were removed, counted, and then incubated for 24 hrs. The supernatant was analyzed for TNF-alpha, NO, IL-10, and MIP-2.


METHODS
University research laboratory.


METHODS
Male Sprague-Dawley rats (n = 16).


METHODS
Administration of heat before endotoxin infusion.


RESULTS
Alveolar-arterial oxygen gradient was lower in the heat stress group at 4 and 5 hrs after endotoxemia. Plasma and alveolar macrophage supernatant concentrations of TNF-alpha, NO, and IL-10 were not affected by heat. Plasma and alveolar macrophage supernatant MIP-2 concentrations were higher in endotoxemic rats receiving heat pretreatment compared with controls.


CONCLUSIONS
Our study demonstrates that heat leads to pulmonary protection of short duration in severe endotoxemia. This protection was not mediated by plasma TNF-alpha, IL-10, or NO. Contrary to our hypothesis, pretreatment with heat increased rather than decreased the plasma MIP-2 concentration and alveolar macrophage production of MIP-2 in endotoxemia. The mechanism of heat-conferred pulmonary protection in endotoxemia remains unclear. Alveolar macrophages do not produce IL-10 in endotoxemia. The increased MIP-2 production by heated alveolar macrophages was not attributable to alterations in production of either TNF-alpha or IL-10. The significance of increased MIP-2 by endotoxin-exposed alveolar macrophages in heated rats is unknown.
Heidemann
S M
SM
Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, USA.
Lomo
L
L
Ofenstein
J P
JP
Sarnaik
A P
AP
D000818:Animals; D054426:Chemokine CXCL2; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000276:immunology*; D005334:Fever / Q000276:immunology*; D018882:Heat Stress Disorders / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology*; D015846:Monokines / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011659:Pulmonary Gas Exchange; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; D016207:Cytokines; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide