Introduction

In developed countries, approximately 4-5% of the population suffers from some form of autoimmune disease, making the latter a major health issue. Cytokines play a crucial role in the regulation of immune and inflammatory responses and therefore allow the targetting of potential candidate genes for diseases involving immune dysfonction. The broad spectrum of IL-10 activity in the immune system suggests that this cytokine is a key component in protective and pathological responses. This pleiotropic cytokine is mainly produced "endogenously" by Th2 cells, monocytes/macrophages and B cells (genetic influence?).1 In addition, "exogenous" IL-10 related cytokines can also be produced by several viruses such as herpes virus or pox virus genera (environmental influence?).2

IL-10 is highly regarded as being involved in anti-inflammatatory and immunosuppressive functions, in large part on the basis of results obtained using animal models.3 IL-10 also contributes to enhancing B cell survival and proliferation, and antibody production. By studying its direct effects on individuals' immune cell populations, it has been observed that IL-10 can act at different phases of the immune response. Thus, it suppresses several cell immune functions, and therefore can prevent the proliferation of autoreactive lymphocytes. For example, IL-10 prevents the migration of dendritic cells to lymph nodes4 and the production of proinflammatory chemokines.5 IL-10 also inhibits the synthesis of IL-12 and tumor necrosis factor (TNF)-a, and leads to the down-regulation of major histocompatibility complex (MHC) class II antigens and costimulatory molecules in antigen-presenting cells.5 The presence of IL-10 interferes with Th1 cell functions. It blocks the activation of the synthesis of interferon (IFN)-y and proinflammatory cytokines.6,7 Anergic T cells are obtained when these T cells produce IL-10.8 In animal models of autoimmunity, recent data shows that IL-10 regulates autoreactive T cells and inhibits the progression of autoimmune diabetes9 and of experimental

Interleukin-10, edited by Francesco M. Marincola. ©2006 Eurekah.com.

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Figure 1. Schematic representation of IL-10 gene promoter polymorphisms. The locations of the various known single nucleotide polymorphisms (SNPs) are defined upstream of the transcription start site (ATG), as are the two CA-repeat microsatellites, IL-10.R and IL-10.G. Bold letters correspond to polymorphisms usually used to investigate an association with disease susceptibility. Positive and negative regulatory regions, described previously by Kube et al27 are schematically represented by shadowy and grey boxes respectively.

Figure 1. Schematic representation of IL-10 gene promoter polymorphisms. The locations of the various known single nucleotide polymorphisms (SNPs) are defined upstream of the transcription start site (ATG), as are the two CA-repeat microsatellites, IL-10.R and IL-10.G. Bold letters correspond to polymorphisms usually used to investigate an association with disease susceptibility. Positive and negative regulatory regions, described previously by Kube et al27 are schematically represented by shadowy and grey boxes respectively.

autoimmune encephalomyelitis (EAE).10 In this last model of EAE, only high levels of IL-10 were induced in the protocol used. Nevertheless, the presence of other cytokines produced endogenously within the inflammatory site may increase11 or impair12 such modulating effects of IL-10. Thus, the transgenic expression of IL-10 in mice can exacerbate inflammatory processes13 and autoimmune diseases.14

The expression of IL-10 appears to be strictly regulated. The levels of its constitutive expression in normal cells are very gene exhibits substantial polymorphism in the promoter region, which appears to be correlated with variations in transcription.16,17 Several groups have investigated IL-10 promoter polymorphisms, which may result in an altered level of expression. Therefore, the IL-10 gene must be considered as important candidate for conferring susceptibility and severity to the development of autoimmunity. In this review, IL-10 gene structure and polymorphisms, and the links between IL-10 polymorphisms and auto-immune diseases are summarized.

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