The beneficial effects of immunostimulation in posttraumatic sepsis.
Granulocyte macrophage-colony stimulating factor (GM-CSF) is a myelopoietic cytokine that may enhance immune mechanisms directed against bacterial infection. Injury is associated with an increased incidence of such infection. This study assessed the potential immunostimulatory role of GM-CSF in the injured host predisposed to infection. Six- to eight-week old female CD-1 mice underwent trauma and were then randomized to received either GM-CSF or saline vehicle control intraperitoneally for 5 days. They then received a septic challenge in the form of a cecal ligation and puncture. Following this, assessment was made of survival and bacterial growth indices in blood cultures, and peritoneal cells were harvested for assessment of peritoneal immune function. Intraperitoneal GM-CSF administration daily for 5 days following injury was associated with significantly greater survival following cecal ligation and puncture compared to controls (40 vs 5%, P < 0.05). There was a significant increase in peritoneal cell yields in the GM-CSF group compared to the control group (11 +/- 1 x 10(6) vs 8 +/- 1 x 10(6) P < 0.05). PMA-stimulated macrophages released significantly higher amounts of both superoxide anion (1.4 +/- 0.1 vs 0.93 +/- 0.1, P < 0.05) and tumor necrosis factor (5.2 +/- 0.6 vs 2.6 +/- 0.7, P < 0.03) and significantly less nitric oxide compared to the control group (175 +/- 8 vs 267 +/- 24, P < 0.003). Finally, bacterial growth indices were significantly reduced following GM-CSF administration (194 +/- 6 vs 218 +/- 4, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Austin
O M
OM
Department of Surgery, Beaumont Hospital, RCSI, Dublin, Ireland.
Redmond
H P
HP
Watson
W G
WG
Cunney
R J
RJ
Grace
P A
PA
Bouchier-Hayes
D
D
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D015993:Life Tables; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010529:Peritoneal Cavity / Q000473:pathology; D010538:Peritonitis / Q000517:prevention & control; D011994:Recombinant Proteins; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology; D013481:Superoxides / Q000378:metabolism; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000150:complications*
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor