Kidney-Yang Deficiency Syndrome (KYDS) is closely bound up with the immune response of immunocompromised patients. The study is to investigate whether retinoic acid-inducible gene-I (RIG-I)-mediated innate immune responseparticipates in the development of KYDS in rats and evaluate the effect of Yougui pill (YGP) on the response in KYDS rats. KYDS rats were induced by intramuscular injection of hydrocortisone at the dose of 10 mg/kg/d for 15 days. YGP at concentrations of 2.43 g/kg/d and 4.86 g/kg/d were administered intragastrically to KYDS rats for 30 days. The resultsshowed that the body weight, urinary 17-hydroxycorticosteroid (17-OHCS) level, spleen size and spleen index in KYDS rats were significantly decreased compared with healthy control rats, while YGP treatment reversed them towards normal level in a dose-dependent manner. Moreover, KYDS challenge not only strikingly increased the mRNA and protein expression levels of RIG-I, tripartite motif containing 25 (TRIM25), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) but alsomarkedly enhanced the endogenous RIG-I polyubiquitination levels. Whereas, YGP treatment effectively reversed this tendency in a dose-dependent manner. In conclusion, these findings revealed that RIG-I-mediated innate immune response was closely bound up with the development of KYDS. And YGP exhibited certain anti-inflammatory effects on KYDS rats via inhibiting the RIG-I-mediated innate immune response
