Induction of cytokines and anti‐cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis

We have recently described the induction of anti‐cytokine autoantibodies (Aabs) in the serum as a novel mechanism for cytokine regulation during bacterial infections. Here we use the infant rat‐model of Haemophilus influenzae type b (Hib) meningitis to examine the induction of five potentially important cytokines and their autoantibody responses in the CSF. Protein levels of the cytokines interferon‐gamma (IFN‐γ), tumour necrosis factor‐alpha (TNF‐α), transforming growth factor‐beta (TGF‐β), IL‐4 and IL‐10 were detected at day 3 post‐inoculation (p.i.) with maximum induction at day 8. Thereafter, these levels of cytokines had become undetectable. Increased Aab titres to these cytokines, except IL‐4, were registered with peak levels between days 7 and 9. Upon re‐inoculation with Hib at day 30, regeneration of Aabs was recorded 7 days later (i.e. at day 37). To control the specificity of these Aabs, preincubation of the CSF with a cytokine inhibited the binding effects of that particular cytokine, but not those of any other cytokine. Aabs dose‐dependently inhibited IFN‐γ‐induced MHC expression by peritoneal macrophages and TNF‐α‐mediated L929 cytotoxicity. Our data demonstrate for the first time the existence of the anti‐cytokine antibodies in the CSF of the meningitis Hib model. Furthermore, the data present a role for the Aabs in cytokine regulation, which is consistent with the previously demonstrated effects of the Aabs in the serum.