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 (A abs) in the serum as a novel mechanism for cytokine regulation during bacte rial infections. Here we use the infant rat-model of Haemophilus influenzae type b (Hib) meningitis to examine the induction of five potentially impor tant cytokines and their autoantibody responses in the CSF. Protein levels of the cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-4 and IL-10 we re 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 leve ls between days 7 and 9. Upon re-inoculation with Hib at day 30, regenerati on of Aabs was recorded 7 days later (i.e. at day 37). To control the speci ficity of these Aabs, preincubation of the CSF with a cytokine inhibited th e binding effects of that particular cytokine, but not those of any other c ytokine. Aabs dose-dependently inhibited IFN-gamma-induced MHC expression b y peritoneal macrophages and TNF-alpha-mediated L929 cytotoxicity. Our data demonstrate for the first time the existence of the anti-cytokine antibodi es 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 prev iously demonstrated effects of the Aabs in the serum.