title: Production of tumor necrosis factor by human cells in vitro and in vivo, induced by group B streptococci.
abstract: 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.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
authors.forename: P A
authors.initials: PA
authors.lastname: Williams
authors.forename: J F
authors.initials: JF
authors.lastname: Bohnsack
authors.forename: N H
authors.initials: NH
authors.lastname: Augustine
authors.forename: W K
authors.initials: WK
authors.lastname: Drummond
authors.forename: C E
authors.initials: CE
authors.lastname: Rubens
authors.forename: H R
authors.initials: HR
authors.lastname: Hill
mesh_terms: 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*
chemical_list: D014409:Tumor Necrosis Factor-alpha