Role of p38/ERK Pathway in IL‐12 Restoration of T Cell IL‐2/IFN‐γ Production Following Alcohol (EtOH) Intoxication and Injury

Abstract

The mechanism by which EtOH potentiates post burn pathogenesis remains unknown. We have shown that EtOH intoxication prior to burn injury potentiates the suppression of mesenteric lymph node (MLN) T cell IL‐2/IFN‐γ and enhances bacterial translocation. The suppression in T cell was accompanied with a decrease in p38 and ERK activation. Since we also found a decrease in IL‐12, this study examined whether IL‐12 restitution restores T cell IL‐2/IFN‐γ following EtOH and burn injury and whether p38/ERK pathway is involved in IL‐12 restoration of IL‐2/IFN‐γ. Male rats (250g) were gavaged with 5 ml of 20% EtOH 4h prior to ~12.5% total body surface area burn or sham injury. Rats were sacrificed on day one after injury. MLN T cells were isolated, stimulated with anti‐CD3 in the absence or presence of recombinant (r) IL‐12 (10ng/ml) for 5 min and lysed for p38 and ERK1/2 measurements. In some experiments, T cells were cultured for 48h with or without the inhibitors of p38 (10μM SB203580) or ERK (50μM PD98059). Results indicate that the incubation of T cells with rIL‐12 prevents the suppression of T cell IL‐2/IFN‐γ following EtOH and burn injury. Furthermore, IL‐12 normalizes both p38 and ERK activation in T cells, but results obtained using p38 and ERK inhibitors indicate that the restoration of ERK and not p38 is critical to IL‐12‐mediated restoration of T cell IL‐2/IFN‐γ production following EtOH and burn injury. (R01AA015731–01A2)