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

AIDS. 2005 Oct 14;19(15):1601-6. doi: 10.1097/01.aids.0000183520.52760.ef.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • AIDS-Related Opportunistic Infections / immunology*
  • AIDS-Related Opportunistic Infections / virology
  • Adult
  • Alternative Splicing
  • Antiretroviral Therapy, Highly Active
  • Antitubercular Agents / therapeutic use
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4 Lymphocyte Count
  • Cross-Sectional Studies
  • Female
  • Gene Expression
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / genetics
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Treatment Outcome
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / immunology*
  • Viral Load


  • Antitubercular Agents
  • Interleukin-4
  • Interferon-gamma