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

Abstract

SUMMARYWe 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-g), tumour necrosis factor-alpha (TNF-a), transforming growth factor-beta (TGF-b), 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-g-induced MHC expression by peritoneal macrophages and TNF-a-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.

Disseminated Mycobacterium avium Complex Infection in a Patient with Autoantibody to Interferon-.GAMMA.

“…Regarding this finding, Bakhiet et al (10) proposed that the induction of anti-cytokine autoantibodies to tumor necrosis factor (TNF)-α and IFN-γ might occur as mechanisms for cytokine regulation in experimental bacterial meningitis in rats. Patel et al (6) …”

Potential Role of Human Brain Microvascular Endothelial Cells in the Pathogenesis of Brain Abscess: Inhibition of Staphylococcus aureus by Activation of Indoleamine 2,3-Dioxygenase

“…Besides its direct inhibitory effect on microbial growth, IFN-g can modulate the production of TNF-a, another cytokine possibly protective against bacterial infection [21]. IFN-g and TNF-a have been detected in cerebrospinal fluid of meningitis patients as well as in experimentally induced meningitis, indicating an involvement in CNS-infections [3,16,23]. Fig.…”

Brain network alterations in the inflammatory soup animal model of migraine

“…Furthermore, the issue of inflammatory processes can be considered in the following manner: (1) local inflammation that activates nociceptive processes as assessed by electrophysiological measures of trigeminal system afferents (Levy et al, 2007; Oshinsky, 2014; Strassman et al, 1996); and (2) more diffuse effects of the inflammation on brain systems (ref). There are a number of approaches to evaluating the latter including: (a) direct measures of inflammatory systems using PET markers of glial activity (Ji et al, 2013; Loggia et al, 2015; Owen and Matthews, 2011)with and without IS application; and (b) measures of CSF markers of inflammation (viz., cytokines (Bakhiet et al, 1998) or other markers of neuroimmune activation (viz., neopterin (Murr et al, 2002). …”