The Journal of Immunology, 2006, 176: 5137.
Copyright © 2006 by The American Association of Immunologists
Comment on "Pretreatment Intracerebral and Peripheral Blood Immune Responses in Vietnamese Adults with Tuberculous Meningitis: Diagnostic Value and Relationship to Disease Severity and Outcome"
Michael Eisenhut
Institute of Child Health, University of Liverpool, Liverpool, United Kingdom
Simmons et al. (1) found that in patients with tuberculous meningitis (TBM) CSF concentrations of IL-6 were independently associated with significant neurological deficit (British Medical Research Council grade III). This finding suggested an involvement of IL-6 in the pathogenesis of neurological deficit in TBM. Previous research linked IL-6 to poor outcome in acute ischemic stroke (2), which is a common complication of TBM (3). The authors did not comment on a recent finding in patients with TBM that may explain the increased IL-6 levels in patients with neurological deficit. In a prospective study in children with TBM in Kakinada, India, we found that patients with neurological deficit had significantly higher CSF adenosine deaminase (ADA) levels compared with controls with TBM without this complication (4). ADA is produced by T lymphocytes and monocytes, and it has recently been found that, after binding to the adenosine receptor on dendritic cells, it interacts with CD26 receptors on lymphocytes. This costimulatory signal caused a marked increase in the production of IL-6 by lymphocytes (5). IL-6 and ADA levels correlated significantly in pleural fluid of patients with tuberculous pleuritis (6). Further support for the importance of ADA in IL-6 induction and microvascular compromise comes from trials of ADA inhibition by pentostatin in mice in which ADA inhibition reduced circulating IL-6 levels and parameters of endothelial injury and microvascular dysfunction (7). Future studies need to explore the potential of ADA inhibition with pentostatin, which is approved for use in humans (8), in supportive treatment of TBM.
The author declares that he has no competing interests.
References
- Simmons, C. P., G. E. Thwaites, N. T. H. Quyen, E. Torok, D. M. Hoang, T. T. H. Chau, P. P. Mai, N. T. N. Lan, N. H. Dung, H. T. Quy, et al 2006. Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome. J. Immunol. 176: 2007-2014. [Abstract/Free Full Text]
- Waje-Andreassen, U., J. Krakenes, E. Ulvestad, L. Thomassen, K.-M. Myhr, J. Aarseth, C. A. Vedeler. 2005. IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol. Scand. 111: 360-365. [Medline]
- Chan, K. H., R. T. Cheung, R. Lee, W. Mak, S. L. Ho. 2005. Cerebral infarcts complicating tuberculous meningitis. Cerebrovasc. Dis. 19: 391-395. [Medline]
- Jakka, S., S. Veena, A. R. M. Rao, M. Eisenhut. 2005. Cerebrospinal fluid adenosine deaminase levels and adverse neurological outcome in pediatric tuberculous meningitis. Infection 33: 264-266. [Medline]
- Pacheco, R., J. M. Martinez-Navio, M. Lejeune, N. Climent, H. Oliva, J. M. Gatell, T. Gallart, J. Mallol, C. Lluis, R. Franco. 2005. CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse. Proc. Natl. Acad. Sci. USA 102: 9583-9588. [Abstract/Free Full Text]
- Yokoyama, A., M. Maruyama, M. Ito, N. Kohno, K. Hiwada, S. Yano. 1992. Interleukin 6 activity in pleural effusion: its diagnostic value and thrombopoietic activity. Chest 102: 1055-1059. [Abstract/Free Full Text]
- Cohen, E. S., W. R. Law, C. R. Easington, K. Q. Cruz, B. A. Nardulli, R. A. Balk, J. E. Parrillo, S. M. Hollenberg. 2002. Adenosine deaminase inhibition attenuates microvascular dysfunction and improves survival in sepsis. Am. J. Respir. Crit. Care Med. 166: 16-20. [Abstract/Free Full Text]
- Brogden, R. N., E. M. Sorkin. 1993. Pentostatin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in lymphoproliferative disorders. Drugs 46: 652-677. [Medline]
