Causes of immune dysfunction in hyperbilirubinemia model rats

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-TAKI protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method. After 24 hours of model establishment, serum 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-TAKI 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-kappa B signal pathways activation and aggravate inflammatory reaction, thus caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.