Cytokines do play a role in pathogenesis of tuberculous meningitis: A prospective study from a tertiary care center in India

Background: Though animal studies have suggested a role for proinflammatory cytolcines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results. Aim and objectives: To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity. Patients and methods: Present study included 146 patients with TBM (90- Definite TBM; 56- Probable TBM), diagnosed according to criteria laid by Ahuja et al. which were modified to include CSF nucleic acid based tests. Serum (n = 146) and CSF (n = 140) levels of various proinflammatory cytolcines (IL-1 beta, IL-2, IL-6, TNF-alpha. and IFN gamma) were compared between TBM patients and healthy volunteers (n = 99). These levels were correlated with various clinical, radiological and CSF parameters of TBM patients. Results: Proinflammatory cytokines include cytokines which promote systemic inflammation. In current study, the serum and CSF levels of various cytokines (IL-2, IL-4, IL-6, IL-1 beta, IFN-gamma and TNF-alpha) were significantly elevated in TBM patients compared to controls. A significant correlation was found between a) Higher stage of TBM and various cytolcines (except for serum IL-6 and CSF IFN-gamma); b) High CSF TNF-alpha, IL-4 and IL-1 beta with severity of hydrocephalus; c) High CSF alp and IFN-gamma with presence of exudates on MRI; d) Serum and CSF levels of all cytokines with poor outcome as determined by death or as defined by S and E ADL (Schwab and England activities of daily living) score or by GOS (Glasgow outcome scale) (except for interferon gamma); and e) Serum and CSF IL-4 and 1113 with presence of infarcts on MRI brain. Conclusion: Proinflammatory cytokines play an important role in the pathogenesis of TBM and contribute significantly towards severity of disease. (C) 2017 Elsevier B.V. All rights reserved.