Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)—possible immunosuppressive role of IFN-α in HIV infection

Abstract

SUMMARYInterferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-a, IFN-g, 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-a compared with healthy controls (n 19), with particularly high levels in advanced disease. HAART induced a marked decrease in levels of both IFN-a, neopterin and IP-10, though not to normal concentrations. In contrast, IFN-g levels were low throughout the study, and not different from controls. While neopterin and IP-10 remained signi®cantly decreased compared with baseline levels throughout the study, IFN-a levels returned to baseline at the end of the study. Persistently high IP-10 and IFN-a levels were associated with immunological treatment failure and even high baseline levels of IFN-a appeared to predict immunological relapse. Furthermore, we found a markedly suppressive effect of exogenously added IFN-a on phytohaemagglutinin-stimulated lymphocyte proliferation in both patients and controls, and this suppressive effect seemed not to involve enhanced lymphocyte apoptosis. Our ®ndings suggest a pathogenic role of IFN-a in HIV infection, which may be a potential target for immunomodulating therapy in combination with HAART.

Interleukin-10 enhances the oxidized LDL-induced foam cell formation of macrophages by antiapoptotic mechanisms

“…After culturing for 48 h, DNA fragmentation in apoptotic cells was assessed by the TUNEL assay (15).…”

Immunological Profiles in HIV Positive Patients with or without Opportunistic Infections and the Influence of Highly Active Antiretroviral Therapy: A Systematic Review and Update

“…Among the research articles that satisfied the criteria for inclusion, 4 were cross-sectional based in nature [5,21,31,32], 8 were longitudinal studies [27,[33][34][35][36][37][38][39]], 5 were prospective cohort studies [40-44] whereas 2 studies involved use of both cross-sectional and longitudinal study designs [26,45]. Table 1 presents the types of studies, population among other variables included in our review.…”

“…Similarly, the contribution of antiretroviral treatment towards expression of multiple plasma cytokines during HIV has previously been described, though not well elucidated [35]. Standard antiretroviral treatment for management of HIV comprises of at least three antiretroviral drugs that suppress HIV replication.…”

“…A study by Stylianou et al [35] involving HIV positive cohorts, revealed elevated IP-10 and IFN-α levels in HIV subjects relative to healthy controls prior to HAART initiation. Upon therapeutic intervention, levels of both cytokines significantly declined although not to normal concentrations [35]. This observation may be an indication of host immune recovery that regulates inflammatory episodes associated with these cytokines.…”

“…For instance, elevated levels of this chemokine have been reported in different viral infections such as severe influenza infection [2,87], West Nile virus infection [88], acute and chronic Hepatitis C [89], showcasing its involvement in immune responses during viral infections. However, during HIV mono-infection, levels of IP-10 are upregulated compared to healthy individuals [35,90,91]. More importantly, the raised IP-10 levels during HIV are inversely correlated with CD4 + T cell counts and directly with viral load thus promoting HIV replication [41,92].…”