Abstract
Purpose To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury.Methods Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination.Results Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05).Conclusions Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.
Highlights
Systemic inflammatory response syndrome is a phenomenon in which various stimuli- such as severe trauma, sepsis, acute mesenteric ischemia and major surgery- induce a widespread activation of inflammatory cascades leading to multi-organ failure[1]
Our findings indicate that adalimumab treatment significantly reduces circulating cytokines (TNF-α and IL-6), which are released as a response to lipopolysaccharide administration in rats
In animals that are subjected to lipopolysaccharide, adalimumab treatment resulted in a significant reduction in serum levels of cardiac injury markers and amelioration of histopathologic signs of myocardial injury
Summary
Systemic inflammatory response syndrome is a phenomenon in which various stimuli- such as severe trauma, sepsis, acute mesenteric ischemia and major surgery- induce a widespread activation of inflammatory cascades leading to multi-organ failure[1]. In the course of major surgical procedures including cardiac surgery with cardiopulmonary bypass and aortic aneurysm repair, the disruption of endothelial cell barrier may permit the passage of endotoxins through the mucosal epithelium to the adjacent tissues or distal organs and provoke a systemic inflammatory response leading to increased postoperative complications[3,4,5,6]. Increased myocardial and serum levels of TNF-α and IL-6 during Lps-mediated systemic inflammatory responses have shown to be associated with both cellular and functional cardiac deterioration[10,11]. Inhibition of TNF-α has been observed to attenuate endotoxin induced myocardial injury[12,13]
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