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-l-infected individuals show a reduced ab ility to secrete IFN-alpha. We investigated an association between an imbalance of type1/type2 cytokines and the production of IFN-alpha in HIV-1 infection. We used whole blood culture to study the cytokine pro duction 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-a was obtained in patients with a predomina nt IL-4 production (IL-4 > IFN-gamma), and we found a positive con-ela tion 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 investigate d the role of T-cell-derived cytokines in the in vitro production of I FN-alpha by PBMC from eight healthy donors, activated with Sendai Viru s or HSV-1, Whereas type 2 cytokines (IL-4, IL-13) inhibited virus-ind uced IFN-alpha synthesis, on the contrary, type 1 cytokines (IL-2, IFN -gamma) enhanced it. A disarray in the T-cell-derived cytokine respons e may play a role in the defect of IFN or production in HIV-l-infected individuals. Further investigations are needed to explore this hypoth esis.