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)
Mendez
M V
MV
Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Molloy
R G
RG
O'Riordain
D S
DS
Holzheimer
R G
RG
Nestor
M S
MS
Obando
A
A
Saporoschetz
I
I
Schoof
D D
DD
Mannick
J A
JA
Rodrick
M L
ML
D000818:Animals; D002056:Burns / Q000276:immunology / Q000401:mortality*; D016207:Cytokines / Q000096:biosynthesis; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018805:Sepsis / Q000276:immunology / Q000401:mortality*; D015996:Survival Rate
D016207:Cytokines; D007376:Interleukin-2