Does granulocyte colony-stimulating factor ameliorate the proinflammatory response in human meningococcal septic shock?
OBJECTIVE
To test the hypothesis that granulocyte colony-stimulating factor acts cooperatively with interleukin-10 in down-regulating monocyte function in severe meningococcal septic shock. 1) We quantified the plasma levels of granulocyte colony-stimulating factor, interleukin-10, Neisseria meningitidis lipopolysaccharide and the number of N. meningitidis DNA copies in 28 patients with systemic meningococcal disease. 2) We studied the inhibitory effect of recombinant human granulocyte colony-stimulating factor on normal human monocytes stimulated with purified meningococcal lipopolysaccaride. 3) We monitored the inhibitory effects of endogenously produced granulocyte colony-stimulating factor and interleukin-10 in meningococcal shock plasmas on monocytes.


METHODS
Comparative, experimental study.


METHODS
University Hospital and laboratory.


METHODS
Twenty-eight patients with systemic meningococcal disease, 13 with persistent shock, 7 died, and 15 without shock.


RESULTS
The median levels of granulocyte colony-stimulating factor in shock and nonshock patients were 1.7 x 10(6) and 8.1 x 10(2) pg/mL; interleukin-10, 2.1 x 10(4) and 4 x 10(1) pg/mL; number of N. meningitidis DNA copies, 2.9 x 10(7) and <10(3)/mL; and lipopolysaccharide, 105 and <0.04 endotoxin units/mL, respectively. The plasma levels of granulocyte colony-stimulating factor were reduced by 50% within 4 to 6 hrs after initiation of antibiotic treatment. In model experiments with lipopolysaccharide-stimulated human monocytes, recombinant human granulocyte colony-stimulating factor and interleukin-10 reduced the release of tumor necrosis factor-alpha by mean 30% and 92%, respectively. When plasmas from three shock patients were depleted of native granulocyte colony-stimulating factor or interleukin-10 by immunoprecipitation, no increase in tumor necrosis factor-alpha release occurred after removal of granulocyte colony-stimulating factor, whereas removal of interleukin-10 increased the tumor necrosis factor-alpha release eight-fold.


CONCLUSIONS
Although granulocyte colony-stimulating factor in plasma increases by five orders of magnitude in patients with meningococcal shock, the anti-inflammatory effect on patients' monocytes is uncertain.
Rojahn
Astrid
A
Department of Pediatrics, Ullevål University Hospital, Oslo, Norway.
Brusletto
Berit
B
Øvstebø
Reidun
R
Haug
Kari B F
KB
Kierulf
Peter
P
Brandtzaeg
Petter
P
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008589:Meningococcal Infections / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009345:Neisseria meningitidis; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000378:metabolism* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor