Production of interleukin-4, interferon (IFN)-gamma and IFN-alpha in human immunodeficiency virus-1 infection: an imbalance of type 1 and type 2 cytokines may reduce the synthesis of IFN-alpha.
Interferon-alpha (IFN-alpha) is an important molecule in the antiviral response, but cells from HIV-1-infected individuals show a reduced ability to secrete IFN-alpha. We investigated an association between an imbalance of type 1/type2 cytokines and the production of IFN-alpha in HIV-1 infection. We used whole blood culture to study the cytokine production profile, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), in response to HIV-1 antigens and to study the Sendai Virus and HSV-1-induced-production of IFN-alpha in seven HIV-1-infected patients. An impaired synthesis of IFN-alpha was obtained in patients with a predominant IL-4 production (IL-4 > IFN-gamma), and we found a positive correlation between the ex vivo production of IFN-alpha and the IFN-gamma/IL-4 ratio but not with the HIV RNA copy number in plasma. We investigated the role of T-cell-derived cytokines in the in vitro production of IFN-alpha by PBMC from eight healthy donors, activated with Sendai Virus or HSV-1. Whereas type 2 cytokines (IL-4, IL-13) inhibited virus-induced IFN-alpha synthesis, on the contrary, type 1 cytokines (IL-2, IFN-gamma) enhanced it. A disarray in the T-cell-derived cytokine response may play a role in the defect of IFN-alpha production in HIV-1-infected individuals. Further investigations are needed to explore this hypothesis.
Hober
D
D
Laboratoire de Virologie, Institut Gernez-Rieux, CHU, Lille, France.
Benyoucef
S
S
Chehadeh
W
W
Chieux
V
V
De La Tribonniere
X
X
Mouton
Y
Y
Bocket
L
L
Wattre
P
P
D000328:Adult; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology
D016898:Interferon-alpha; D015847:Interleukin-4; D007371:Interferon-gamma