Timing of Insulin therapy Affect the inflammatory response in Endotoxemic Rats

皱波¹ 虞文魁¹ 李维勤¹ 李宁¹ 黎介寿¹
南京军区南京总医院外科ICU

Objective:. The aim of the present study was to determine whether timing of insulin administration influences the hepatic and serum proinflammatory and anti-inflammatory cytokines during endotoxemia stimulated by LPS.
Materials and Methods: 81 Male Sprague Dawley rats were divided in 9 groups: Group A was sham control group (rats were treated with saline and without insulin or LPS); Group B was LPS group (rats were treated with LPS and without insulin); In Group C,D,E,F,G,H and I, insulin was given on 30 min pre LPS administrated and hour 0, 1, 3, 6, 12 and 24hr after the induction of endotoxemia, in respectively. Hepatic and serum proinflammatory cytokines IL-1β, IL-6 and TNF-a, and antiinflammatory cytokines IL-10 were detected on 24 and 48 hours after the induction of endotoxemia.
RESULTS: Compared with sham control rats, serum concentrations of proinflammatory cytokines IL-1β, IL-6 and TNF-a and anti-inflammatory cytokine IL-10 were significantly increased on 24 and 48 hrs after induction of endotoxemia. Similarly, LPS administration also significantly increased the hepatic IL-1β, TNF-aIL-6 and IL-10 protein concentration on 48 hrs after LPS injection. Compared with levels in endotoxemic animals receiving saline, on 24 and 48hrs after LPS injection, insulin administrated ahead of 6hrs after LPS injection significantly decreased the serum IL-1β, IL-6 and TNF-a concentration (P<0.05), and significantly increased anti-inflammatory cytokine IL-10 concentration (P<0.05); And, hepatic IL-1β and IL-6 expression were (P<0.05) significantly decreased compared with levels in endotoxemic animals receiving saline. But, the significant decrease of hepatic TNF-a expression and significant increase of hepatic IL-10 were only seen in the animals in which insulin was administrated at 30mins pre LPS or coadministrated with LPS. Insulin administrated post of 6 hrs after LPS injection lost the ability to significantly reduced serum or hepatic IL-1β, TNF-a, and IL-6 concentration.
Conclusions: Insulin has a protective role in systemic inflammatory response syndrome (SIRS) related to sepsis, such as down-regulation of pro-inflammatory cytokines, and up-regulation anti-inflammatory cytokine production. However, timing of insulin administrated may change its affect of inflammatory response in endotoxemic rats. Insulin administrated post of 6 hrs after LPS injection lost the ability to protect in inflammatory response related to sepsis.