Production of tumor necrosis factor by human cells in vitro and in vivo, induced by group B streptococci.
Tumor necrosis factor alpha (TNF alpha) has been implicated as one of the major mediators of the gram-negative septic shock syndrome. In our studies, group B streptococci (GBS) induced the production of TNF alpha by human mononuclear cells in a dose- and time-dependent manner. Human mixed mononuclear cell cultures exposed to an encapsulated (657.6 +/- 71.3 pg/ml; n = 30 preparations) or an unencapsulated transposon mutant of type III GBS (755.8 +/- 54.7 pg/ml; n = 9) produced similar amounts of TNF alpha. Isolated monocytes and culture-derived macrophages produced higher amounts of TNF alpha (1565 +/- 211 and 1790 +/- 928 pg/ml respectively) in response to GBS than did mixed mononuclear cell cultures. In response to GBS, mixed mononuclear cells from neonates produced significantly more TNF alpha (729.1 +/- 45 vs 520.3 +/- 47.2 pg/ml; p = 0.004) than did cells from adults. Examination of specimens from patients with neonatal GBS disease revealed detectable levels of TNF alpha (7 to 424 pg/ml) in the serum of 5 of 10 patients with sepsis, in 5 of 5 urine samples from infants with sepsis, and in the cerebrospinal fluid of 1 patient with meningitis. These results suggest both a major role for TNF alpha in the pathogenesis of human neonatal GBS sepsis and shock and a potential role for immunotherapy directed against this cytokine in this fulminant neonatal bacterial infection.
Williams
P A
PA
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
Bohnsack
J F
JF
Augustine
N H
NH
Drummond
W K
WK
Rubens
C E
CE
Hill
H R
HR
D000328:Adult; D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D013290:Streptococcal Infections / Q000209:etiology / Q000378:metabolism*; D013292:Streptococcus agalactiae; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha