Corticosteroids in Tuberculosis

Cisneros, Jennifer R; Murray, Kim M.

doi:10.1177/106002809603001115

Cited by 57 publications

(29 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The inflammatory response is driven by cytokines, including tumor necrosis factor alpha (TNF-␣), produced by mononuclear phagocytes in response to infection with M. tuberculosis (8,13,23,24). Immunomodulatory drugs, such as corticosteroids, that reduce cytokine production, thereby dampening the inflammatory response, are often used in addition to the conventional antibiotic treatment (1,4,7,22).…”

mentioning

confidence: 99%

Use of IMiD3, a Thalidomide Analog, as an Adjunct to Therapy for Experimental Tuberculous Meningitis

Tsenova

Mangaliso

Muller³

et al. 2002

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Tuberculous meningitis (TBM), the most severe form of Mycobacterium tuberculosis infection in humans, is associated with significant morbidity and mortality despite successful treatment with antituberculous drugs. This is due to the irreversible brain damage subsequent to the local inflammatory response of the host to M. tuberculosis. Corticosteroids have been used in conjunction with antituberculous therapy in an attempt to modulate the inflammatory response, but this strategy has been of limited success. Therefore, we examined whether combining antituberculous drugs with the immunomodulatory drug thalidomide or with a new thalidomide analog, immunomodulatory drug 3 (IMiD3), would be effective in reducing morbidity and mortality in an experimental rabbit model of TBM. Intracisternal inoculation of 5 ؋ 10 4 CFU of Mycobacterium bovis Ravenel in rabbits induced progressive subacute meningitis characterized by high cerebrospinal fluid (CSF) leukocytosis, protein influx, release of tumor necrosis factor (TNF), substantial meningeal inflammation, and mortality by day 28. Treatment with antituberculous drugs or with antituberculous drugs plus thalidomide improved the clinical course of disease somewhat and increased survival to about 50%. In contrast, treatment with antituberculous drugs in combination with IMiD3 limited pathological neurologic changes and resulted in marked improvement (73%) in survival. IMiD3 treatment was also associated with reduced leukocytosis in the CSF and significantly lower levels of TNF in CSF and plasma. Histologically, the meningeal inflammation in animals treated with antituberculous drugs plus IMiD3 was considerably attenuated compared to that of the other treatment groups. These results suggest a potential role for IMiD3 in the management of TBM in patients.

show abstract

mentioning

confidence: 99%

Use of IMiD3, a Thalidomide Analog, as an Adjunct to Therapy for Experimental Tuberculous Meningitis

Tsenova

Mangaliso

Muller³

et al. 2002

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Clinical conditions that induce impaired cell-mediated immunity like AIDS, malignancy, and immunosuppressive therapy result in impaired MHC class II-mediated delayed-type hypersensitivity (DTH) reaction (1,2). Moreover, long-standing clinical observations have established that certain diseases that do not induce a generalized immunosuppressive state, also induce impaired DTH reaction to specific antigens, a state clinically defined as "anergy."…”

Section: Introductionmentioning

confidence: 99%

IL-10–producing T cells suppress immune responses in anergic tuberculosis patients

Boussiotis¹,

Tsai²,

Yunis³

et al. 2000

J. Clin. Invest.

362

283

View full text Add to dashboard Cite

IntroductionClinical conditions that induce impaired cell-mediated immunity like AIDS, malignancy, and immunosuppressive therapy result in impaired MHC class II-mediated delayed-type hypersensitivity (DTH) reaction (1, 2). Moreover, long-standing clinical observations have established that certain diseases that do not induce a generalized immunosuppressive state, also induce impaired DTH reaction to specific antigens, a state clinically defined as "anergy." Classical paradigms of these diseases include tuberculosis (TB), sarcoidosis, and Hodgkin's disease.TB is the leading cause of death from infectious diseases worldwide (3), accounting for eight million new cases and three million deaths annually (6). The lethality of TB is due to both the absence of an effective vaccine and to the poor understanding of how the mycobacteria escape immune surveillance. Anergy in the setting of TB refers to the paradoxical absence of dermal reactivity to intradermal injection with tuberculin purified protein derivative (PPD) in infected persons. It occurs in about 15% of patients with active pulmonary disease and is associated with absence of granuloma formation and all other manifestations of cellular hypersensitivity (3-5). We thus chose to examine the biochemical events that regulate the induction of TB anergy since this understanding may also provide insights into the pathophysiology of this disease.Anergy in vitro and its in vivo counterpart, tolerance, are immunologically defined as the inability of antigenspecific T cells to produce IL-2 and clonally expand on rechallenge with fully competent antigen-presenting cells (APC) (7,8). Induction of anergy is an active signaling process induced when T-cell receptor (TCR) is ligated by antigen without costimulation. Anergy can also be induced in the presence of costimulation if the TCR is ligated by superantigen or by altered peptide ligands that bear a single amino acid substitution in the sequence of the agonistic peptide (9). Although quite distinct, these three approaches to induce anergy appear to share common biochemical events characterized by hypophosphorylation of TCRζ and defective activation of ZAP-70 and Ras (10-15), indicating the generalized significance of these findings in the anergic state. Recently, IL-10 in The lethality of Mycobacterium tuberculosis remains the highest among infectious organisms and is linked to inadequate immune response of the host. Containment and cure of tuberculosis requires an effective cell-mediated immune response, and the absence, during active tuberculosis infection, of delayedtype hypersensitivity (DTH) responses to mycobacterial antigens, defined as anergy, is associated with poor clinical outcome. To investigate the biochemical events associated with this anergy, we screened 206 patients with pulmonary tuberculosis and identified anergic patients by their lack of dermal reactivity to tuberculin purified protein derivative (PPD). In vitro stimulation of T cells with PPD induced production of IL-10, IFN-γ, and proliferation in PPD +...

show abstract

“…10 Disruption of immune function, either by drugs, 20 therapeutic monoclonal antibodies, 21,22 or other disease, 3 increases the likelihood of active TB disease, suggesting that the immune system is responsible for the control of the infection and prevention of active disease in the majority of infected individuals. However, generation of host immune responses to fight TB is not without risk.…”

Section: Tb Immunologymentioning

confidence: 99%