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SEVERE IMBALANCE IN INTERLEUKIN-18 AND INTERLEUKIN-18 BINDING PROTEIN IN PATIENTS WITH HIV/AIDS
A Iannello, O Debbeche, S Samarani, Z Almalte, E Toma, A Ahmad
Objectives: Interleukin-18 (IL-18), originally discovered and named as the IFN-gamma-inducing factor, is a multifunctional and pleiotropic cytokine. Its activity is regulated by IL-18 binding protein (IL-18BP), a naturally occurring cytokine that binds IL-18 and inhibits its biological activity. We have earlier reported increased concentrations of circulating IL-18 in HIV-infected AIDS patients compared with healthy HIV-seronegative control individuals. However little is known about the production of IL-18BP in AIDS patients. Because of its relevance to IL-18 regulation, we were interested in knowing how HIV infection affects IL-18BP production and IL-18-mediated immune responses.
Methods: In order to study balance between these two mediators in AIDS patients, we measured IL-18 and IL-18BP in the sera of 32 HIV-infected persons using commercial ELISA kits and compared them with a similar number of sera from age-matched HIV-seronegative healthy subjects using standard statistical methods.
Results: Our data show that sera from HIV-infected patients had 2.5 to 3 fold higher levels of IL-18 as compared to the sera from healthy subjects. In contrast to this, the levels of IL-18BP were significantly decreased in the sera from HIV-infected persons as compared to healthy subjects. Furthermore, a significant positive correlation existed between IL-18 and IL-18BP in sera from healthy persons. This correlation was not observed in the sera from HIV-infected AIDS patients. Consequently the mean ratio between IL-18 and IL-18BP was significantly increased in the infected subjects as compared to the control subjects.
Conclusions: The increase in IL-18 production accompanied by a relative decrease in the production of IL-18BP represents an imbalance between these two soluble factors in HIV-infected patients. This uncoordinated production of IL-18 and IL-18BP may contribute further to IL-18-induced immunopathology in HIV-infected AIDS patients and may contribute to the HIV-induced pathogenesis.