Effect of PD-1 Blockade on Neonatal Sepsis and Septic Kidney Injury in Mice

Background: Blocking the Programmedcelldeath-1 (PD-1) pathway can improve the prognosis and survival of patients with sepsis, and affect the occurrence of kidney injury in sepsis, but the mechanisms are still unclear. In this study we explored the effects of PD-1 blocking on neonatal sepsis and sepsis kidney injury, and aim to explore whether the kidney changes are mediated by glycolysis pathway. Methods: C57BL/6 newborn mice at 7 days post birth (P7) were selected and randomly divided into four groups: Anti- PD-1-LPS group, neonatal mice were i.p. injected with anti PD-1 antibody (10mg/kg), 24 hours later followed i.p. injected with lipopolysaccharides(LPS) (15mg/kg); Anti-PD-1-NS group; NS-LPS group; and control group (NS-NS group). After injecting LPS or physiological saline, all mice were subdivided into 6 hour group, 12 hour group, and 24 hour group. Blood and renal tissue were collected separately. ELISA was performed to determine the soluble PD-1 (sPD-1) and IL-6 in serum. Renal tissue morpholog by HE, and the expression of PD-1 and PFKFB3 in renal tissue by IHC. Results: The serum IL-6 levels in the NS-LPS group were significantly higher than those in the NS-NS group, while the serum IL-6 levels in the Anti-PD-1-LPS group were also significantly higher than those in the NS-LPS group. The proximal tubule epithelial cells in the Anti-PD-1-NS group showed mild edema changes, and the proximal tubule epithelial cells in the NS-LPS group showed serious damage, while the proximal tubule damage in the Anti-PD-1-LPS group was reduced. The expression of PD-1 in the kidneys of the NS-LPS group was significantly increased, the expression of PFKFB3 was not significantly different. The expression of PD-1 in Anti-PD-1-LPS group was decreased, while PFKFB3 expression was significantly increased (Fig 1). Conclusion: Serum sPD-1 may involved in the neonatal sepsis. PD- 1 blockade can significantly increase the expression level of IL-6. PD-1 blockade can alleviate renal tubular injury in neonatal sepsis, which may be mediated by changes in glycolysis. Funding: Government Support – Non-U.S.