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.


METHODS
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.
Dheda
Keertan
K
Centre for Infectious Diseases and International Health, Royal Free and UCL Medical School, University College London, London, UK.
Chang
Jung-Su
JS
Breen
Ronan A M
RA
Haddock
Jamanda A
JA
Lipman
Marc C
MC
Kim
Louise U
LU
Huggett
Jim F
JF
Johnson
Margaret A
MA
Rook
Graham A W
GA
Zumla
Alimuddin
A
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D000328:Adult; D017398:Alternative Splicing; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*; D019562:Viral Load
D000995:Antitubercular Agents; D015847:Interleukin-4; D007371:Interferon-gamma