Lymphokine activated killer cells enhance IL-2 prevention of sepsis-related death in a murine model of thermal injury.

It has previously been shown by this laboratory that immunomodulation of thermally injured animals with low-dose interleukin-1 (IL-2) and indomethacin (Indo) improves survival following septic challenge. Lymphokine-activated killer (LAK) cells have been shown to be effective in certain viral infections and to act in synergy with IL-2 in the treatment of certain types of cancer. We have studied the effect of LAK cells in combination with IL-2 and Indo in a murine model of thermal injury and sepsis. Male A/J mice received a 25% scald burn injury or sham burn and were randomized into five groups: (a) sham/vehicle, (b) burn/vehicle, (c) burn/IL-2 (250 U) + Indo (5 micrograms), (d) burn/LAK cells (2 x 10(6) cells), or (e) burn/LAK cells+IL-2+Indo and were treated accordingly for 6 days following injury. LAK cells were generated by in vitro IL-2 treatment of syngeneic spleen cells for 72 hr and cytotoxic activity was confirmed by standard 51Cr release assay using natural killer (NK)-sensitive and NK-resistant targets. In the groups receiving LAK cells they were administered on Day 1 and Day 6 postinjury. On Day 10, septic challenge by cecal ligation and puncture (CLP) or splenectomy, for in vitro studies, was performed. Five-day survival after CLP was 80% in the sham/vehicle group compared to 0% in the burn/vehicle group (P < 0.01). IL-2/Indo and LAK/IL-2/Indo improved survival to 25% (P < 0.05) and 57.1% (P < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)