Interleukin-10 protects against lethality of intra-abdominal infection and sepsis.
The aim of this study was to determine whether interleukin-10 would alter locally derived and systemic proinflammatory cytokine expression and protect from the lethality of cecal ligation and puncture. Three groups of Sprague-Dawley rats were used. Group 1 underwent cecal manipulation. Groups 2 and 3 underwent cecal ligation and puncture. Group 2 received intraperitoneal saline injections beginning 1 hour after cecal ligation and puncture and every 3 hours thereafter for 24 hours. Group 3 received intraperitoneal interleukin-10 one hour after cecal ligation and puncture and every 3 hours thereafter. Animals were killed at 6 and 24 hours after cecal ligation and puncture or sham operation. Serum tumor necrosis factor-alpha (TNF-alpha) levels were determined by enzyme-linked immunosorbent assay. TNF-alpha messenger RNA expression was determined by reverse transcriptase-polymerase chain reaction using Beta-actin as the internal standard. There was a twofold increase (P <0.001) in TNF-alpha mRNA in the liver at 6 and 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. There was a twofold increase (P <0.05) in TNF-alpha mRNA in the lung observed only at 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. Serum levels of TNF-alpha were elevated at 6 hours in control animals, and this effect was abolished by the administration of interleukin-10. There was no difference in mortality rates at 6 hours (0% for all groups); however, at 24 hours 57% (4/7) mortality was observed in group 2 vs. 0% (0/20) in groups 1 and 3. Interleukin-10 given after the onset of cecal ligation and puncture protects against the lethality of intra-abdominal sepsis.
Rongione
A J
AJ
Department of Surgery, UCLA, Los Angeles, California 90024, USA.
Kusske
A M
AM
Kwan
K
K
Ashley
S W
SW
Reber
H A
HA
McFadden
D W
DW
D018784:Abdominal Abscess / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D002432:Cecum / Q000601:surgery; D005260:Female; D016753:Interleukin-10 / Q000494:pharmacology*; D008026:Ligation; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D011677:Punctures; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10