Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods:A total of 60 newborn SD rats were equally randomized into normal saline(NS) group,LPS control group,bilirubin control group,low-dose group and high-dose group.After anesthesia,0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups;1 h later,the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups.After 5 or 24 hours of model establishment,spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method.After 24 hours of model establishment,scrum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results:In contrast to low-dose bilirubin,high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS.After 5 hours of model establishment,compared with NS group.MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced(P<0.05).In high-dose group,inflammotory factors levels and CD8~+T cells percentage were all higher than LPS control and NS group(P<0.05),while CD4~+ T cells percentage was lower than NS group(P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF- κB signal pathways activation and aggravate inflammatory reaction,thus caused immunosuppression with inflammation cascade,which resulted in the immune dysfunction. Objective: To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia. Methods: A total of 60 newborn SD rats were equally randomized into normal saline (NS) group, LPS control group, bilirubin control group, low-dose group and high- dose group. After anesthesia, 0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups; 1 h later, the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1 mg / kg LPS for the other groups. After 5 or 24 hours of model establishment, spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemistry and TUNEL method. After 24 hours of model establishment, scrum inflammatory Factors levels and T cell subsets distribution were determined by ELISA and flow cytometry. Results: In contrast to low-dose bilirubin, high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS. After 5 hours of model establishment, compared with NS group. MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced (P <0.05) .In high-dose group, inflammotory factors levels and CD8 + While CD4 + T cells percentage was lower than NS group (P <0.05) .Conclusions: High-concentration plasma bilirubin in coordination with LPS could inhibit NF - κB signal pathways activation and aggravate inflammatory reaction, which caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.