title: Antibodies to tumor necrosis factor-alpha: use as adjunctive therapy in established group B streptococcal disease in newborn rats.
abstract: Group B Streptococcus (GBS) is the leading cause of neonatal sepsis. Adjunctive therapies are being sought to improve the outcome. Because increased blood levels of tumor necrosis factor (TNF)-alpha may play a role in the development of sepsis and an adverse outcome thereof, we evaluated the potential use of antibodies against TNF-alpha as adjunctive therapy of GBS sepsis. Using a neonatal rat model of GBS sepsis, we measured serum levels of TNF-alpha. Levels of TNF-alpha were significantly increased beginning 12 h after GBS inoculation and remained significantly increased at 30-36 h. We then examined the use of adjunctive therapy with antibody to TNF-alpha in animals with established GBS sepsis using polyclonal rabbit antirecombinant mouse TNF-alpha antiserum. Twelve hours after GBS inoculation, animals received a single dose of antibody to TNF-alpha or normal rabbit serum, and penicillin therapy (twice a day for 3 d) was begun. Animals receiving penicillin and antibody to TNF-alpha had a survival rate of 52% (13 of 25) versus 29% (7 of 24) for animals receiving penicillin and normal rabbit serum. Thus, the use of antibodies directed against TNF-alpha may have a role as adjunctive therapy of established GBS sepsis in the newborn infant.
authors.affiliation: Department of Pediatrics, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Givner
authors.forename: L
authors.initials: L
authors.lastname: Gray
authors.forename: T M
authors.initials: TM
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D051379:Mice; D010400:Penicillin G / Q000008:administration & dosage; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D013292:Streptococcus agalactiae; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D010400:Penicillin G