Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection.
Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-alpha, IFN-gamma, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV-infected patients had raised levels of both IP-10 and IFN-alpha compared with healthy controls (n = 19), with particularly high levels in advanced disease. HAART induced a marked decrease in levels of both IFN-alpha, neopterin and IP-10, though not to normal concentrations. In contrast, IFN-gamma levels were low throughout the study, and not different from controls. While neopterin and IP-10 remained significantly decreased compared with baseline levels throughout the study, IFN-alpha levels returned to baseline at the end of the study. Persistently high IP-10 and IFN-alpha levels were associated with immunological treatment failure and even high baseline levels of IFN-alpha appeared to predict immunological relapse. Furthermore, we found a markedly suppressive effect of exogenously added IFN-alpha on phytohaemagglutinin-stimulated lymphocyte proliferation in both patients and controls, and this suppressive effect seemed not to involve enhanced lymphocyte apoptosis. Our findings suggest a pathogenic role of IFN-alpha in HIV infection, which may be a potential target for immunomodulating therapy in combination with HAART.
Stylianou
E
E
Section of Clinical Immunology and Infectious Diseases and Research Institute for Internal Medicine, Medical Department, Rikshospitalet, Oslo, Norway. eva.stylianou@klinmed.uio.no
Aukrust
P
P
Bendtzen
K
K
Müller
F
F
Frøland
S S
SS
D019380:Anti-HIV Agents / Q000627:therapeutic use; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016898:Interferon-alpha / Q000276:immunology*; D019798:Neopterin / Q000276:immunology
D019380:Anti-HIV Agents; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016898:Interferon-alpha; D019798:Neopterin