Inhibition of Tumor Necrosis Factor-a and Inducible Nitric Oxide Synthase Correlates with the Induction of IL-10 in Septic Rats Undergoing Laparotomy and Laparoscopy
Abstracts
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Proinflammatory mediators are implicated in the host response to stress. The inflammatory response has been reported to be higher after open surgery than laparoscopic surgery. The purpose of this study was to investigate the inflammatory reponse of tumor necrosis factor a (TNF), inducible nitric oxide synthase (iNOS), and the anti-inflammatory response of Interleukin 10 (IL-10) after laparotomy and CO2 laparoscopy in a rat model of endotoxin shock. METHODS Rats were anesthetized and injected intraperitoneally with 1.5 mg/kg of lipopolysaccaride (LPS) 10 min before surgical intervention. Animals (n=5) were divided into 4 groups: (1) 4 cm laparotomy for 30 min. (2) 6 mm Hg pneumoperitoneum for 30 min. (3)LPS injection alone (4) Anesthesia alone. Animals were sacrificed and blood and liver samples were analyzed at 2, 4, and 8 hrs after LPS injection. Statistical comparison was by Analysis of Variance and Newman-Keuls test with significance p < 0.05. RESULTS Serum TNF levels peaked at 2 hrs and were significantly depressed in laparotomy (82%) and laparoscopy (78%) animals compared to unoperated controls (p<0.05). Serum IL-10 levels were significantly higher at 2 hrs in the laparotomy (2.5-fold increase) and laparoscopy (2.6-fold increase) groups compared to LPS alone, but remained significantly higher only in the laparotomy group at 4 hrs after LPS injection (p<0.05). The expression levels of LPS-induced iNOS mRNA and protein in the laparotomy and laparoscopy groups was significantly inhibited at 4 hrs (45% and 47%, respectively) and 8 hrs (41% and 45%, respectively) compared with the unoperated group (p<0.05). There were no significant differences in the LPS-induced TNF and iNOS comparing lapaotomy and laparoscopy groups (p>0.05). The induction of IL-10 correlated temporally with the suppression of serum TNF and hepatic iNOS. CONCLUSIONS These findings suggest that endogenous production of IL-10 may play a role in downregulating TNF and iNOS expression in septic rats undergoing lapaotomy and laparoscopy. The absence of differences between laparotomy and laparoscopy in the present study may be related to magnitude of the septic insult and requires further investigation. |
