Induction of the stress response increases interleukin-6 production in the intestinal mucosa of endotoxaemic mice.
Previous studies suggest that production of interleukin-6 (IL-6) is increased in the intestinal mucosa during sepsis and endotoxaemia. We tested the hypothesis that mucosal IL-6 production during endotoxaemia is increased further by the heat-shock (stress) response. The stress response was induced in mice by hyperthermia (rectal temperature of 42 degrees C for 3 min) or by intraperitoneal injection of sodium arsenite (10 mg/kg). At 2 h after induction of the stress response, groups of mice were injected subcutaneously with endotoxin (10 mg/kg) or sterile saline. IL-6 mRNA and protein levels in the jejunal mucosa were determined by an RNase protection assay and an ELISA respectively, and levels of hsp72 (heat-shock protein of 72 kDa) were determined by Western blot analysis. Hyperthermia and sodium arsenite increased hsp72 levels in the intestinal mucosa. IL-6 concentrations were increased in the jejunal mucosa of endotoxaemic mice, and this effect of endotoxaemia was potentiated by the stress response. Mucosal IL-6 mRNA levels were increased in endotoxaemic mice, and were increased further by the stress response. Thus it is concluded that mucosal IL-6 production during endotoxaemia may be further stimulated by the stress response. Increased IL-6 levels in the intestinal mucosa may be a potential mechanism by which the stress response exerts a protective effect during sepsis and endotoxaemia.
Wang
Q
Q
Shriners Hospital for Children, Cincinnati, OH, USA.
Sun
X
X
Pritts
T A
TA
Wong
H R
HR
Hasselgren
P O
PO
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D019446:Endotoxemia / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D018869:Heat-Shock Response / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology*; D007583:Jejunum / Q000276:immunology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D012333:RNA, Messenger / Q000032:analysis
D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; D012333:RNA, Messenger