HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simmons, C. P. Articles by Farrar, J. Search for Related Content PubMed PubMed Citation Articles by Simmons, C. P. Articles by Farrar, J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DEXAMETHASONE

The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses¹

Cameron P. Simmons^2,3,*, Guy E. Thwaites^3,*, Nguyen Than Ha Quyen^3,*, Tran Thi Hong Chau^3,, Pham Phuong Mai^3,, Nguyen Thi Dung^3,, Kasia Stepniewska^3,, Nicholas J. White^3,, Tran Tinh Hien^3, and Jeremy Farrar^3,*

^* Oxford University Clinical Research Unit, Hospital for Tropical Diseases, and Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; and Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Outcome from tuberculous meningitis (TBM) is believed to be dependent on the severity of the intracerebral inflammatory response. We have recently shown that dexamethasone improved survival in adults with TBM and postulated that the clinical effect would be associated with a measurable systemic and intracerebral impact on immunological markers of inflammation. Prolonged inflammatory responses were detected in all TBM patients irrespective of treatment assignment (placebo or dexamethasone). The inflammatory response in the cerebrospinal fluid was characterized by a leukocytosis (predominantly CD3⁺CD4⁺ T lymphocytes, phenotypically distinct from those in the peripheral blood), elevated concentrations of inflammatory and anti-inflammatory cytokines, chemokines, and evidence of prolonged blood-brain barrier dysfunction. Dexamethasone significantly modulated acute cerebrospinal fluid protein concentrations and marginally reduced IFN- concentrations; other immunological and routine biochemical indices of inflammation were unaffected. Peripheral blood monocyte and T cell responses to Mycobacterium tuberculosis Ags were also unaffected. Dexamethasone does not appear to improve survival from TBM by attenuating immunological mediators of inflammation in the subarachnoid space or by suppressing peripheral T cell responses to mycobacterial Ags. These findings challenge previously held theories of corticosteroid action in this disease. An understanding of how dexamethasone acts in TBM may suggest novel and more effective treatment strategies.

This article has been cited by other articles:

				S. McGee and J. Hirschmann Use of Corticosteroids in Treating Infectious Diseases Arch Intern Med, May 26, 2008; 168(10): 1034 - 1046. [Abstract] [Full Text] [PDF]

				R. B. Rock, M. Olin, C. A. Baker, T. W. Molitor, and P. K. Peterson Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects Clin. Microbiol. Rev., April 1, 2008; 21(2): 243 - 261. [Abstract] [Full Text] [PDF]

				T. R. Sterling, T. Martire, A. S. de Almeida, L. Ding, D. E. Greenberg, L. A. Moreira, H. Elloumi, A. P.V. Torres, C. C. Sant'Anna, E. Calazans, et al. Immune Function in Young Children With Previous Pulmonary or Miliary/Meningeal Tuberculosis and Impact of BCG Vaccination Pediatrics, October 1, 2007; 120(4): e912 - e921. [Abstract] [Full Text] [PDF]

				J. E. Harris, M. Fernandez-Vilaseca, P. T. G. Elkington, D. E. Horncastle, M. B. Graeber, and J. S. Friedland IFN{gamma} synergizes with IL-1{beta} to up-regulate MMP-9 secretion in a cellular model of central nervous system tuberculosis FASEB J, February 1, 2007; 21(2): 356 - 365. [Abstract] [Full Text] [PDF]

				J. E. Harris, R. K. Nuttall, P. T. Elkington, J. A. Green, D. E. Horncastle, M. B. Graeber, D. R. Edwards, and J. S. Friedland Monocyte-Astrocyte Networks Regulate Matrix Metalloproteinase Gene Expression and Secretion in Central Nervous System Tuberculosis In Vitro and In Vivo J. Immunol., January 15, 2007; 178(2): 1199 - 1207. [Abstract] [Full Text] [PDF]

				S. L. Walker and D. N. J. Lockwood The clinical and immunological features of leprosy Br. Med. Bull., November 7, 2006; (2006) ldl010v1. [Abstract] [Full Text] [PDF]

				C. P. Simmons, 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. Pretreatment Intracerebral and Peripheral Blood Immune Responses in Vietnamese Adults with Tuberculous Meningitis: Diagnostic Value and Relationship to Disease Severity and Outcome J. Immunol., February 1, 2006; 176(3): 2007 - 2014. [Abstract] [Full Text] [PDF]