Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease

Background: Immune restoration disease (IRD) is an adverse consequence of antiretroviral therapy, where the restored pathogen-specific response causes immunopathology. Mycobacteria are the pathogens that most frequently provoke IRD and mycobacterial IRD is a common cause of morbidity in HIV-infected...

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Main Authors: Lim, A., D'Orsogna, L., Price, Patricia, French, M.
Format: Journal Article
Published: 2008
Online Access:http://hdl.handle.net/20.500.11937/29786
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author Lim, A.
D'Orsogna, L.
Price, Patricia
French, M.
author_facet Lim, A.
D'Orsogna, L.
Price, Patricia
French, M.
author_sort Lim, A.
building Curtin Institutional Repository
collection Online Access
description Background: Immune restoration disease (IRD) is an adverse consequence of antiretroviral therapy, where the restored pathogen-specific response causes immunopathology. Mycobacteria are the pathogens that most frequently provoke IRD and mycobacterial IRD is a common cause of morbidity in HIV-infected patients co-infected with mycobacteria. We hypothesised that the excessive effector immune response in mycobacterial IRD reflects impaired regulation by IL-10. Results: We studied two patients who experienced mycobacterial IRD during ART. One patient developed a second episode of IRD with distinct clinical characteristics. Findings were compared with patients 'at risk' of developing IRD who had uneventful immune recovery. Peripheral blood mononuclear cells (PBMC) from all subjects were stimulated with mycobacterial antigens in the form of purified protein derivative (PPD). Supernatants were assayed for IFN? and IL-10. In response to PPD, PBMC from IRD patients generated IFN? during the first IRD episode, whilst cells from non-IRD controls produced more IL-10. Conclusion: We present preliminary data from two HIV-infected patients showing an imbalance between IFN? and IL-10 responses to mycobacterial antigens during mycobacterial IRD. Our findings suggest that imbalanced effector and regulatory cytokine responses should be investigated as a cause of IRD. © 2008 Lim et al; licensee BioMed Central Ltd.
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spelling curtin-20.500.11937-297862017-09-13T15:27:12Z Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease Lim, A. D'Orsogna, L. Price, Patricia French, M. Background: Immune restoration disease (IRD) is an adverse consequence of antiretroviral therapy, where the restored pathogen-specific response causes immunopathology. Mycobacteria are the pathogens that most frequently provoke IRD and mycobacterial IRD is a common cause of morbidity in HIV-infected patients co-infected with mycobacteria. We hypothesised that the excessive effector immune response in mycobacterial IRD reflects impaired regulation by IL-10. Results: We studied two patients who experienced mycobacterial IRD during ART. One patient developed a second episode of IRD with distinct clinical characteristics. Findings were compared with patients 'at risk' of developing IRD who had uneventful immune recovery. Peripheral blood mononuclear cells (PBMC) from all subjects were stimulated with mycobacterial antigens in the form of purified protein derivative (PPD). Supernatants were assayed for IFN? and IL-10. In response to PPD, PBMC from IRD patients generated IFN? during the first IRD episode, whilst cells from non-IRD controls produced more IL-10. Conclusion: We present preliminary data from two HIV-infected patients showing an imbalance between IFN? and IL-10 responses to mycobacterial antigens during mycobacterial IRD. Our findings suggest that imbalanced effector and regulatory cytokine responses should be investigated as a cause of IRD. © 2008 Lim et al; licensee BioMed Central Ltd. 2008 Journal Article http://hdl.handle.net/20.500.11937/29786 10.1186/1742-6405-5-9 unknown
spellingShingle Lim, A.
D'Orsogna, L.
Price, Patricia
French, M.
Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
title Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
title_full Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
title_fullStr Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
title_full_unstemmed Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
title_short Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
title_sort imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
url http://hdl.handle.net/20.500.11937/29786