Granulocyte-macrophage colony-stimulating factor modulates immune function and improves survival after experimental thermal injury.
Thermal injury is associated with reduced colony-stimulating activity, which correlates with increased susceptibility to infection. To assess the effect of therapeutic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF), 8-week old anaesthetized mice were subjected to either a 20 per cent body surface burn or a sham burn. Animals were subsequently treated with either vehicle or a range of doses of GM-CSF (10-1000 ng) with or without indomethacin (5 micrograms). Sepsis was induced by caecal ligation and puncture on day 10 after injury. Survival was significantly better in animals treated with 200 ng GM-CSF on days 5-9 after the burn. Concanavalin A-stimulated T cell proliferation and interleukin (IL) 2 production were significantly depressed after burn injury. In vivo therapy with 200 ng GM-CSF, however, led to a significant improvement in both of these parameters of T cell function. These data suggest that GM-CSF has a potential therapeutic role in the prevention of death from burn sepsis and appears to act, at least in part, by restoring defective T cell proliferation and IL-2 production.
Molloy
R G
RG
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Holzheimer
R
R
Nestor
M
M
Collins
K
K
Mannick
J A
JA
Rodrick
M L
ML
D000818:Animals; D002056:Burns / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D015431:Weight Loss
D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007213:Indomethacin