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

Andrew Lim¹ , Lloyd D'Orsogna² , Patricia Price¹^,3 and Martyn A French¹^,3

¹School of Pathology and Laboratory Medicine, University of Western Australia, Level 2 Medical Research Foundation, Rear 50 Murray Street, Perth 6000, Australia

²Department of Clinical Immunology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands 6009, Australia

³Department of Clinical Immunology and Immunogenetics, Level 2 North Block, Royal Perth Hospital, Wellington Street, Perth 6000, Australia

author email corresponding author email

AIDS Research and Therapy 2008, 5:9doi:10.1186/1742-6405-5-9


Published:	29 April 2008

Abstract

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 IFNγ and IL-10. In response to PPD, PBMC from IRD patients generated IFNγ 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 IFNγ 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.