IL-27 neutralization combined with antibiotics: a promising approach to treating neonatal sepsis

Background Neonatal sepsis is a predominant cause of neonatal mortality and long-term morbidity which severely effects preterm and low birth weight newborns. Antibiotic resistance and long-term developmental issues associated with neonatal sepsis necessitates finding new and improved treatment options. Interleukin-27 (IL-27) has diverse influences on the immune response, is elevated during the neonatal period compared to adulthood, and continues to rise further during infection. In prior work, a neonatal murine sepsis model demonstrated that elevated levels of IL-27 early in life predispose the host to impaired control of the pathogen burden and increased mortality. Mice deficient in IL-27 signaling exhibit reduced mortality, increased weight gain, improved glucose homeostasis, and better control of bacteria with reduced systemic inflammation. Methods This study explored the therapeutic potential of IL-27p28 antibody administration to improve treatment outcomes during murine neonatal sepsis. Sepsis was induced by subcutaneous inoculation of K1-encapsulated Escherichia coli and the neonatal pups were rescued with IL-27p28 monoclonal antibody. We further evaluated the potential for IL-27p28 antibody treatment to augment the protective efficacy of a subclinical dose of gentamicin. Results Pups that received antibody demonstrated superior bacterial clearance and significant weight gain compared to controls during infection. The combination of gentamicin and IL-27p28 antibodies significantly improved bacterial clearance and glucose homeostasis with reduced serum levels of IL-6 and TNF-α compared to gentamicin alone. Moreover, IL-27 antagonization combined with gentamicin minimized vital organ damage and significantly improved the survival rate of infected pups. Conclusion These findings suggest that IL-27p28 antagonization represents a promising therapeutic tool for treatment of neonatal sepsis.