The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Simmons, C. P.
Right arrow Articles by Farrar, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Simmons, C. P.
Right arrow Articles by Farrar, J.
The Journal of Immunology, 2005, 175: 579-590.
Copyright © 2005 by The American Association of Immunologists

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

Cameron P. Simmons2,3,*, Guy E. Thwaites3,*, Nguyen Than Ha Quyen3,*, Tran Thi Hong Chau3,{dagger}, Pham Phuong Mai3,{dagger}, Nguyen Thi Dung3,{dagger}, Kasia Stepniewska3,{ddagger}, Nicholas J. White3,{ddagger}, Tran Tinh Hien3,{dagger} and Jeremy Farrar3,*

* Oxford University Clinical Research Unit, Hospital for Tropical Diseases, and {dagger} Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; and {ddagger} 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-{gamma} 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:


Home page
 Am. J. Respir. Crit. Care Med.Home page
R. J. Wilkinson and C. Lange
Vitamin D and Tuberculosis: New Light on a Potent Biologic Therapy?
Am. J. Respir. Crit. Care Med., May 1, 2009; 179(9): 740 - 742.
[Full Text] [PDF]

Home page
 Arch Intern MedHome page
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]

Home page
 Clin. Microbiol. Rev.Home page
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]

Home page
 PediatricsHome page
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]

Home page
 FASEB J.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 Br Med BullHome page
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]

Home page
 J. Immunol.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.