Production of tumor necrosis factor-alpha and interleukin-6 in mice infected with group B streptococci

Group B streptococci (GBS) are a leading cause of sepsis and meningitis in neonates. Since cytokines are thought to play an important role in septic shock, we have studied serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in BALB/c mice infected with type III GBS. TNF alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial serum samples obtained after infection. After i.p. challenge with an LD50, serum TNF alpha rose above baseline values as early as 3 hr, peaked at 7 hr, and returned to baseline values at 20 hr. IL-6 serum levels rose concomitantly with TNF alpha, peaking 8 hr after challenge. No serum TNF alpha activity was detected in the course of sublethal infections. However, a transient rise in TNF alpha levels was observed after i.v. inoculation of high numbers (greater than or equal to 1 x 10(8) of heat-killed GBS. When groups of mice were injected i.v. with a single dose of anti-TNF alpha rabbit serum 2 hr before challenge with an LD90 or LD30, no effect was noted in terms of survival, although the serum TNF alpha peak was completely abrogated. Serum TNF alpha does not seem to play an obligatory role in GBS-induced lethality of adult mice. However, further studies are needed to assess better the role of this cytokine in the pathogenesis of GBS sepsis.