Short report

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

Andrew Lim , Lloyd D'Orsogna , Patricia Price and Martyn A French

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

Published:	29 April 2008

Abstract (provisional)

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 IFNy and IL-10. In response to PPD, PBMC from IRD patients generated IFNy during the first IRD episode, whilst cells from non-IRD controls produced more IL-10.

Conclusions

We present preliminary data from two HIV-infected patients showing an imbalance between IFNy 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.