Antibodies to tumor necrosis factor-alpha: use as adjunctive therapy in established group B streptococcal disease in newborn rats.
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.
Givner
L B
LB
Department of Pediatrics, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Gray
L
L
O'Shea
T M
TM
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
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D010400:Penicillin G