Inhibition of Interleukin-6 signaling: A novel therapeutic approach to necrotizing enterocolitis

Abstract

ObjectivesThis study investigated the effects of tocilizumab on the prevention and treatment of experimental necrotizing enterocolitis (NEC) in newborn rats. MethodsForty-two newborn Sprague-Dawley rats were randomly separated into three groups: NEC + placebo, NEC + tocilizumab, and the control group. NEC + placebo and NEC + tocilizumab groups were given 1 mg/kg lipopolysaccharide intraperitoneally once only on the first day, were fed with a special rodent formula every 3 h, inhaled 100% CO2 for 10 min, were exposed to cold stress at + 4 °C for 5 min, and 97% O2 for 5 min twice a day for 3 days. NEC + tocilizumab group was treated with 8 mg/kg/day tocilizumab (Actemra®) intraperitoneally, while NEC + placebo group was given intraperitoneal 0.9% saline at a dose of 2 mL/kg/day from the first day to the end of the study. All newborn rats were sacrificed on day 4. Specimens were taken for histopathologic, immunohistochemical and biochemical evaluation from the ileum and proximal colon. ResultsNEC + tocilizumab group had higher weight gain and survival rate compared to NEC + placebo group and clinical sickness score was reduced in NEC + tocilizumab group (p < 0.05). Lower tissue damage and apoptosis were found in the NEC + tocilizumab group compared to the NEC + placebo group (p < 0.01). Tissue Interleukin-6, Interleukin-1β, TNF-α, myeloperoxidase and caspase-3 levels were significantly decreased in the NEC + tocilizumab group (p < 0.01). ConclusionsTocilizumab could be a potential option in the prevention and treatment of NEC.