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 un-interpretable because of failure to distinguish between IL-4 and its splice variant and natural antagonist, IL-4delta2.

OBJECTIVE: To determine Th1 [interferon (IFN)-gamma], IL-4delta2 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-4delta2, IL-4 and IFN-gamma 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-4delta2 or IFN-gamma in blood or lavage. By contrast, the HIV-TB co-infected donors had increased IL-4 and IFN-gamma in both compartments. However the antagonist, IL-4delta2 was increased only in lavage. Consequently the dominant form was IL-4delta2 in lavage, but IL-4 itself in blood. The lung IL-4/IFN-gamma ratio correlated with radiological disease extent. With anti-TB treatment, IL-4 levels did not change whilst IL-4delta2 levels increased significantly.

CONCLUSIONS: IL-4 and its natural antagonist, IL-4delta2 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.