Background and Goal of Study:
Isoflurane modulates the immune response. In addition to regulating immune‑system homeostasis, interleukin (IL)-2 is considered an indicator of functional suppression of T cells because decreased production of IL-2 is associated with increased expression of Casitas B‑lineage lymphoma proto-oncogene (c-Cbl) and Cbl-b in T cells. To evaluate the effect of the inhalational anesthetic agent, isoflurane, on T‑cell function, we assayed IL-2 production and c-Cbl and Cbl-b expression in rat peripheral blood mononuclear cells (PBMCs).

Materials and Methods:
Adult male Sprague–Dawley rats weighing 300–350 g were randomly allocated to the control group (C group), 4 h of isoflurane general anesthesia group (4I group), or 1 day after 4 h of isoflurane general anesthesia group (1D 4I group). Blood was collected by cardiac puncture and PBMCs were isolated. IL-1, IL-2, and IL‑6 mRNA levels and c-Cbl, Cbl-b, protein kinase C (PKC) q, and phospholipase C-g1 (PLC-g1) protein levels in PBMCs were determined by quantitative reverse transcription polymerase chain reaction and immunoblotting, respectively. Moreover, ubiquitination of PKCq and PLC-g1 in PBMCs was assessed by immunoprecipitation.

Results and Discussion:
The mRNA level of IL-2 in rat PBMCs was significantly decreased in the 4I and 1D 4I groups compared with the control group. c-Cbl, Cbl-b, and ubiquitin expression was significantly increased and the zeta-chain-associated protein kinase 70 (ZAP70), PLC-g1, and PKCq protein levels were significantly decreased in the 4I group. Ubiquitination of PLC-g1 and PKCq were also significantly increased in the 4I group.

Conclusion(s):
Isoflurane influences the expression of ubiquitin, c-Cbl, and Cbl-b in rat PBMCs, which indicates suppression of receptor tyrosine kinase signaling pathways. These results suggest that isoflurane suppresses T‑cell function.

03 / Isoflurane Decreases Interleukin-2 Production by Increasing c-Cbl and Cbl-b Expression in Rat Peripheral Blood Mononuclear Cells