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Complementing Heat Stroke: Activation and Amplification of the IL‐6 and Complement System during Heat Stroke Recovery in F344 Rats
Author(s) -
Leon Lisa R,
Duran Rocio M,
Helwig Bryan G.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1201.6
Subject(s) - complement system , immune system , medicine , pathophysiology , endocrinology , sepsis , analysis of variance , gene expression , inflammation , stroke (engine) , immunology , chemistry , gene , biochemistry , mechanical engineering , engineering
The pathophysiological responses to heat stroke (HS) are thought to be due to a systemic inflammatory response syndrome (SIRS) that is initiated by endotoxin leakage across ischemic gut membranes and high IL‐6 production. The complement system (CS) interacts with IL‐6 to modulate the immune response to sepsis, but its role in HS is unknown. We hypothesized that plasma IL‐6 and the liver CS would show a similar time course of activation in male Fischer 344 rats (262 ± 8 g) during 10 days of HS recovery. Plasma IL‐6 (Multiplex; N=9–12/group) and liver expression of 29 genes in the CS pathway (qPCR; N=3/group) were measured at maximum core temperature (Tc,Max=41.8°C; radiotelemetry), 1, 3, 5 and 10 days of HS recovery. Plasma IL‐6 was elevated from Tc,Max to 3 days of recovery with ~100‐fold increase above controls observed on day 1 (4395 ± 201 vs. 41± 22 pg/ml, respectively; ANOVA, P<0.05 ). Plasma IL‐6 was similar to controls on day 5 and 10 of recovery. Liver CS gene expression (5–11 genes/time point) increased ~2 to 6‐fold above controls on day 1, 3 and 5 of recovery, but peak expression was not observed until day 10 with ~20 to 50‐fold increase above controls (ANOVA, P<0.05). This is the first study to demonstrate liver CS activation in response to HS in rats and suggests that IL‐6‐CS interactions may modulate the SIRS during the early days of HS recovery. Research supported by MRMC. Author views not official US Army or DOD policy.