Experimental heatstroke in baboon: analysis of the systemic inflammatory response.
The objective of this study was to analyze the pattern of the inflammatory response to heatstroke in an experimental baboon model with a view to identifying potential target for therapeutic interventions. Blinded analysis of plasma collected from 12 juvenile baboons (Papio hamadryas) in heatstroke was used. Eight anesthetized animals were heat-stressed in an incubator at 44 degrees C to 47 degrees C until rectal temperature was 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. We performed sequential measurement of cytokines. The rectal temperature on completion of heat stress was 42.5 degrees C +/- 0.0 degrees C and 43.3 degrees C +/- 0.1 degrees C in moderate and severe heatstroke, respectively. Heat stress elicited early, simultaneous release of anti-inflammatory cytokines and chemokines (IL-10, IL-1ra, sTNFr I and II, and IL-8). Circulating levels of IL-12p40 were significantly decreased, whereas TNFalpha, IL-1beta, and IL-4 were below the detection limit in all animals. No baboon survived severe heatstroke; there was neurological morbidity without mortality in moderate heatstroke. Nonsurvivors displayed significantly greater activity/alterations in inflammation markers than survivors. Sham-heated animals had no evidence of inflammation activation. These results show that heatstroke activates complex systemic inflammatory and regulatory responses associated with outcome. Further definition of this ambivalent response is needed before identification of target of successful modulation may become possible.
Bouchama
Abderrezak
A
Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia. bouchamaus@yahoo.com
Ollivier
Véronique
V
Roberts
George
G
Al Mohanna
Falah
F
de Prost
Dominique
D
Eldali
Abdelmoneim
A
Saussereau
Elodie
E
El-Sayed
Raafat
R
Chollet-Martin
Sylvie
S
D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018883:Heat Stroke / Q000473:pathology*; D006358:Hot Temperature; D007249:Inflammation / Q000473:pathology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053762:Interleukin-12 Subunit p40; D015847:Interleukin-4 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D010215:Papio; D021122:Protein Subunits / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012795:Sialoglycoproteins / Q000097:blood; D013696:Temperature; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053762:Interleukin-12 Subunit p40; D016209:Interleukin-8; D021122:Protein Subunits; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4