An anti-inflammatory cytokine, Interleukin-11 : A therapeutic target against septic MODS

脓毒症时过度的全身炎症反应会导致严重的组织损伤，导致包括肝脏在内的多个器官衰竭，肝脏是脓毒症的靶器官，也是炎症介质的来源。白介素11(IL-11)是一种多效性细胞因子，通过下调多种促炎介质的表达来抑制炎症反应。虽然已有报道重组人IL-11(rhIL-11)可用于脓毒症的治疗，但IL-11对脓毒症所致肝损伤的治疗作用尚未得到评价。在本研究中，我们研究了重组人白介素11对脓毒症大鼠肝脏损伤的影响。雄性SD大鼠腹腔注射(Ip)。细菌脂多糖(LPS，20 mg/kg)。部分大鼠注射脂多糖后立即给予重组人白介素11(150μg/kg，i.p)治疗。血清丙氨酸转氨酶和天冬氨酸氨基转移酶活性、肝细胞广泛坏死、肿瘤坏死因子-α、诱导型一氧化氮合酶和核因子-αB的κ结合活性均显著升高。相反，从上述指标的改善情况来看，rhIL-11可显著抑制内毒素所致的肝损伤。此外，重组人IL-11治疗可显著降低内毒素诱导的死亡率。这些结果表明，重组人IL-11具有较强的抗炎活性，对脂多糖诱导的脓毒症有保护作用。此外，rhIL-11可能成为治疗脓毒症的新药靶点。

Excessive systemic inflammatory responses in sepsis cause severe tissue injuries leading to multiple organ failures including that of liver, the target organ as well as a source of inflammatory mediators in sepsis. Interleukin-11 (IL-11) is a pleiotropic cytokine that can suppress inflammation through the down-regulation of multiple pro-inflammatory mediators. Although it has been reported that recombinant human IL-11 (rhIL-11) may be useful in the treatment of sepsis, the effect of IL-11 on hepatic injury associated with sepsis has not been evaluated. In the present study, we examined the effect of rhIL-11 specifically on hepatic injury in a rat model of sepsis. Male Sprague-Dawley rats were injected intraperitoneally (i.p.) with bacterial lipopolysaccharide (LPS,20 mg/kg). Immediately after LPS injection, some rats were also treated with rhIL-11 (150μg/kg, i.p.). LPS treatment induced severe hepatic injury as revealed by marked increases in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, extensive hepatocyte necrosis, tumor necrosis factor-α (TNF-α) mRNA, inducible nitric oxide synthase (iNOS) mRNA, and DNA binding activity of nuclear factor-κB (NF-κB). In contrast, rhIL-11 treatment significantly suppressed the LPS-induced hepatic injury, as judged by amelioration of all these indices. In addition, rhIL-11 treatment markedly decreased LPS-induced mortality. These results indicate that rhIL-11 possesses a potent anti-inflammatory activity that plays a protective role in the LPS-induced sepsis. Moreover, rhIL-11 may be a new drug target for sepsis.