Cytokines and Chemokines in HIV Infection

Abstract

Primary human immunodeficiency virus (HIV) infection is associated with a profound activation of the immune system resulting in strong cellular and humoral immune response within a few weeks from the moment of infection (1,2). At the clinical level this may be associated with a mononucleosis-like syndrome with lymph node enlargement and constitutional symptoms. Accordingly, several cytokines are upregulated and detectable during this initial stage of infection, usually enduring for a few weeks and stabilizing within a few months in the majority of individuals, a stage corresponding to a clinically asymptomatic phase. This second period spans several years and is associated with relatively stable levels of plasma-associated HIV RNA (viremia) and slow erosion of peripheral CD4⁺ T cell counts. Finally, in most individuals, opportunistic infections or tumors mark the transition to the acquired immune deficiency syndrome (AIDS) stage resulting in the death of the individual in the absence of potent antiviral agents (2). These three distinct although interconnected stages of disease have been substantially changed in recent years since the introduction of potent antiretroviral regimens known as highly aggressive antiretroviral therapy (HAART) based on combinations of protease inhibitors and inhibitors of the virion-associated reverse transcriptase enzyme (3). Therefore, it is quite difficult at present to investigate the natural history of the disease in industrialized countries, where combination therapy is available, whereas it remains possible in developing countries where antiviral agents are poorly or not accessible at all. It is important to underscore that individuals from the less developed areas of the world, and particularly from Sub-Saharan Africa, are frequently affected by other important infectious diseases and in conditions (i.e., malnutrition) that may profoundly affect cytokine expression (4). In addition, a heterogeneous distribution of viral subtypes may differ in terms of both susceptibility to cytokines for their replication, as suggested by difference in their long terminal repeat (LTR) configuration (5,6) and, potentially for their ability to induce or modulate cytokine expression.