Sepsis and endotoxemia stimulate intestinal interleukin-6 production.
BACKGROUND
Endotoxemia stimulates tumor necrosis factor (TNF) and interleukin-1 (IL-1) production in mucosa of the small intestine, but the effect on IL-6 production is not known. Intestinal IL-6 may be especially important, considering its role in the acute phase response. We tested the influence of endotoxemia and sepsis in mice on intestinal IL-6 and IL-6 messenger RNA (mRNA) levels.


METHODS
Mice were injected with lipopolysaccharide (LPS 10 mg/kg) or saline solution. In some experiments animals were pretreated with indomethacin (5 mg/kg) or N-nitro-L-arginine (NNA, 100 mg/kg) before LPS injection. In other experiments, sepsis was induced by cecal ligation and puncture (CLP); controls were sham operated. Serum and jejunal mucosa were harvested at intervals during 16 hours, and IL-6 levels were determined by enzyme-linked immunosorbent assay. IL-6 mRNA was detected by polymerase chain reaction.


RESULTS
Endotoxemia and sepsis increased serum and mucosal IL-6 and IL-6 mRNA, with maximum levels noted at 1 and 4 hours after LPS and at 8 hours after CLP. Pretreatment of endotoxemic mice with indomethacin or NNA blunted the increase in mucosal IL-6.


CONCLUSIONS
Results suggest that sepsis and endotoxemia stimulate IL-6 production in small intestinal mucosa and that this response may be transcriptionally regulated. The effect of endotoxemia may be partly mediated by prostaglandins and nitric oxide. The results also suggest that the intestinal mucosa may be a participant in the cytokine response, rather than just a passive bystander.
Meyer
T A
TA
Department of Surgery, University of Cincinnati Medical Center, Ohio, USA.
Wang
J
J
Tiao
G M
GM
Ogle
C K
CK
Fischer
J E
JE
Hasselgren
P O
PO
D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D001483:Base Sequence; D015232:Dinoprostone / Q000494:pharmacology; D004731:Endotoxins / Q000097:blood*; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
D004731:Endotoxins; D015850:Interleukin-6; D015335:Molecular Probes; D012333:RNA, Messenger; D009569:Nitric Oxide; D015232:Dinoprostone; D007213:Indomethacin