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-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.
Bakhiet
M
M
Divisions of Neurology and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
Mustafa
M
M
Zhu
J
J
Harris
R
R
Lindquist
L
L
Link
H
H
Diab
A
A
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
D001323:Autoantibodies; D016207:Cytokines