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.