Expression of a novel cytokine, IL-4delta2, in HIV and HIV-tuberculosis co-infection

Background: Correcting the Th2 shift in HIV/AIDS represents a potential intervention strategy. However data on interleukin (IL)-4 expression in HIV or AIDS are uninterpretable because of failure to distinguish between IL-4 and its splice variant and natural antagonist, IL-4δ2. Objective: To determine Th1 [interferon (IFN)-γ], IL-4δ2 and Th2 (IL-4) expression in whole blood and lung lavage from healthy volunteers and in HIV or HIV-tuberculosis (TB) co-infection. Design: Cross-sectional with prospective cohort. Methods: Expression of IL-4δ2, IL-4 and IFN-γ were determined by quantitative real-time PCR, using unstimulated cells from whole blood and lung lavage, in 20 HIV-TB (pulmonary) co-infected patients, 20 matched HIV-positive controls and 20 HIV-negative healthy volunteers. Results were correlated with plasma viral load, CD4 cell counts, radiological scores and response to anti-TB treatment. Results: Compared to HIV negative donors, stable HIV-positive donors did not have increased levels of mRNA encoding IL-4, IL-4δ2 or IFN-γ in blood or lavage. By contrast, the HIV-TB co-infected donors had increased IL-4 and IFN-γ in both compartments. However the antagonist, IL-4δ2 was increased only in lavage. Consequently the dominant form was IL-4δ2 in lavage, but IL-4 itself in blood. The lung IL-4/IFN-γ ratio correlated with radiological disease extent. With anti-TB treatment, IL-4 levels did not change whilst IL-482 levels increased significantly. Conclusions: IL-4 and its natural antagonist, IL-482 and are not upregulated in the absence of opportunistic infection. However in HIV-TB co-infection both cytokines increase in lung, but only IL-4 in the periphery. Further studies are required to determine if IL-4 facilitates systemic HIV progression.