<総説>インスリン依存性糖尿病の病因におけるインターロイキン1およびマクロファージの役割

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A body of data obtained from patients with insulin-dependent diabetes mellitus (IDDM) and its experimental models, Bio-Breeding (BB) rats and nonobese diabetic (NOD) mouse, have established that IDDM is caused by autoimmune destruction of the β cells in the islet. As recent studies have revealed that all the immune phenomena, including autoimmunity, are based upon the interplays of multiple cytokines elaborated by macrophages and lymphocytes, the present review covered recent clinical and experimental works on the pathogenesis of IDDM with special reference to the roles of macrophages and interleukin 1 (IL-1), which is mainly released by macrophages. IL-1 is a multi-functional polypeptide with a wide range of activity in pyrogenesis, inflammation, stress, exercise, sleep and, most importantly, immune responses. In addition, IL-1 potently affects endocrine function as well at multiple levels including the brain, pancreas, thyroid and gonads. In this context, IL-1 exerts two-way effects on islet functions, as a key substance to elicit autoimmune destruction of the β cells and a hormonal modulator of insulin secretion, both leading to the manifestation of diabetes mellitus. IL-1 per se stimulates insulin secretion from the β cells when applied in small doses, but, as a main effect, inhibits substantially the secretion of insulin in the presence of tumor necrosis factor α (TNF). With regard to immune events in the islet caused by macrophages or IL-1,several recent studies have clearly shown that the invasion by small numbers of macrophages associated with the expression of class I major histocompatibility antigen on islet cells is the initial or essential event to further proceed to manifest infiltration by T, natural killer (NK), and B cells. Supporting this, silica which is a toxic substance to macrophages can completely suppress the manifestation of IDDM in experimental models. Thus, although all of T, B and NK cells must work in collaboration for the completion of β-cell destruction to characterize IDDM, the primary importance of macrophages and their product, IL-1 should be appreciated for the initiation of the disease.
近畿大学の論文
1989-12-25

<総説>インスリン依存性糖尿病の病因におけるインターロイキン1およびマクロファージの役割

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