Isoflurane decreases interleukin-2 production by increasing c-Cbl and Cbl-b expression in rat peripheral blood mononuclear cells

Abstract

Objective: To evaluate how isoflurane affects T-cell function by assaying interleukin (IL)-2 production and the expression of two Casitas B-lineage lymphoma (Cbl) family proto-oncogenes (c-Cbl and Cbl-b) in rat peripheral blood mononuclear cells (PBMCs). Methods: Adult male Sprague–Dawley rats were randomly allocated to those that underwent blood collection after brief isoflurane anesthesia (control group), immediately after 4 hours of isoflurane general anesthesia (4I group), and 1 day after 4 hours of isoflurane general anesthesia (1D 4I group). IL-1, IL-2, and IL-6 mRNA levels and c-Cbl and Cbl-b levels in PBMCs were determined by polymerase chain reaction. Ubiquitination of protein kinase Cθ (PKCθ) and phospholipase C-γ1 (PLC-γ1) in PBMCs was assessed by immunoprecipitation. Results: The IL-2 mRNA level in rat PBMCs was significantly lower in the 4I and 1D 4I groups than in the control group. c-Cbl, Cbl-b, and ubiquitin expression was significantly increased and zeta-chain-associated protein kinase 70, PLC-γ1, and PKCθ protein levels were significantly decreased in the 4I group. Ubiquitination of PLC-γ1 and PKCθ was significantly increased in the 4I group. Conclusion: Isoflurane influences ubiquitin, c-Cbl, and Cbl-b expression in rat PBMCs, indicating suppression of receptor tyrosine kinase signaling pathways. These results suggest that isoflurane suppresses T-cell function.