Hematological alterations and splenic T lymphocyte polarization at the crest of snake venom induced acute kidney injury in adult male mice
Snake venom induced acute kidney injury (SAKI) is of great clinical relevance in tropical countries. Involvement of T cell, a key mediator of AKI and its remission, is least explored in SAKI. In the present study the in vivo hematological alterations and associated splenic T cell polarization is probed in order to investigate the immune response at the crest of Russell's viper venom (RVV) induced AKI in experimental murine model. Based on a dose and time kinetic study intra muscular injection dose of 20 μg RVV/100 gm body weight of mice and incubation period of 60 h was selected for induction of SAKI. Renal involvement in SAKI group was confirmed from oliguria, significantly elevated urinary microprotein (p < 0.001), decreased urinary creatinine (p = 0.003) and creatinine clearance (p < 0.001) compared to control. Hematological analyses revealed a significant neutrophilic leukocytosis (p < 0.001) associated with a reduced lymphocyte percentage (p < 0.001) favoring a state of acute inflammation in SAKI group. Immunophenotyping study of splenocytes showed a significant decrease in CD4+/CD8+ ratio (p < 0.001) with a significant increase in regulatory (CD25+FoxP3+) helper and cytotoxic subset of T cell (p < 0.001). Significant increase in IL-10+ regulatory helper and cytotoxic T cell (p < 0.001) further confirmed the internal milieu favoring immunosuppression. Apart from these the CD25−FoxP3+ reservoir regulatory T cells were also found to be significantly elevated in SAKI group compared to that of control (p < 0.001). Taken together, the results of the present study clearly indicated a state of acute inflammation and splenic T cell polarization towards regulatory subset at the crest of SAKI.