title: Induction of cytokines and anti-cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis.
abstract: 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-gamma), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), 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-gamma-induced MHC expression by peritoneal macrophages and TNF-alpha-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.
authors.affiliation: Divisions of Neurology and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bakhiet
authors.forename: M
authors.initials: M
authors.lastname: Mustafa
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: R
authors.initials: R
authors.lastname: Harris
authors.forename: L
authors.initials: L
authors.lastname: Lindquist
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: A
authors.initials: A
authors.lastname: Diab
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000134:cerebrospinal fluid*; D016207:Cytokines / Q000096:biosynthesis / Q000134:cerebrospinal fluid* / Q000276:immunology; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000134:cerebrospinal fluid* / Q000276:immunology; D006193:Haemophilus influenzae / Q000276:immunology*; D008297:Male; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001323:Autoantibodies; D016207:Cytokines