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

Keertan Dheda, Jung Su Chang, Ronan A M Breen, Jamanda A. Haddock, Marc C. Lipman, Louise U. Kim, Jim F. Huggett, Margaret A. Johnson, Graham A W Rook, Alimuddin Zumla

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Abstract

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.

Original languageEnglish
Pages (from-to)1601-1606
Number of pages6
JournalAIDS
Volume19
Issue number15
Publication statusPublished - Oct 14 2005
Externally publishedYes

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Keywords

  • HIV
  • IL-4
  • IL-4δ2
  • Th1/Th2 cells
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dheda, K., Chang, J. S., Breen, R. A. M., Haddock, J. A., Lipman, M. C., Kim, L. U., Huggett, J. F., Johnson, M. A., Rook, G. A. W., & Zumla, A. (2005). Expression of a novel cytokine, IL-4delta2, in HIV and HIV-tuberculosis co-infection. AIDS, 19(15), 1601-1606.