T helper 1/T helper 2 balance and HMG-CoA reductase inhibitors in acute coronary syndrome: statins as immunomodulatory agents?

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Immunity is derived from the Latin word immunitas , which means protection from civic duties and prosecution for a Roman Senator. Today, the principal function of the immune system is the protection of individuals against infectious agents and unsafe foreign (or endogenous) substances. This defence system comprises the early responses, namely innate immunity, and late reactions, called adaptive immunity. Innate immunity is the first line of defence that can be rapidly mobilized to detect pathogen-associated molecular patterns (PAMPs) using PAMP receptors (e.g. scavenger receptors and Toll-like receptors) on the surface of antigen-presenting cells (APCs), such as macrophages and dendritic cells. Adaptive immunity is the antigen-specific immune responses mainly consisting of lymphocytes. There are two types of adaptive immune responses: cell-mediated immunity and humoral immunity ( Figure 1 ). In 1986, Mosmann et al .1 demonstrated for the first time that two types of CD4+ T helper (Th) cells, Th1 and Th2, can be distinguished based on their cytokine profile. The Th1 subset, which drives cell-mediated immunity, is heavily reliant on interferon (IFN)-γ and interleukin (IL)-12 in contrast to the dependence on IL-4 and IL-5 of the Th2 subset, which drives humoral immunity. The effector function of Th1 is the activation of macrophages, neutrophils, and CD8+ cytotoxic T lymphocytes to eliminate phagocytosed microbes and to remove injured tissues. In contrast, the effector function of Th2 is the stimulation of antibody production on B cells and plasma cells to neutralize microbes and their toxins. Multiple sclerosis, rheumatoid arthritis, type-1 diabetes, and graft-versus-host disease (GVHD), are considered as Th1-biased diseases. Allergic disease and systemic lupus erythematosus have been supposed to be Th2-predominant diseases, suggesting that overactivation of either pattern, namely Th1/Th2 imbalance, can cause a specific disease. Atherosclerosis, including acute coronary syndrome (ACS), is now clearly recognized … *Corresponding author. Tel: +81 3 5802 1056; fax: +81 3 5689 0627. E-mail address : shimakaz{at}med.juntendo.ac.jp