Investigation Of The Relationship Between Microvascular Complications Of Diabetes Mellitus And Proinflammatory Cytokine Interleukin-18 Gene Variations

Abstract

Diabetes Mellitus (DM), which is associated with the development of long-term organ disease, is a metabolic disorder that can lead to various complications resulting from high blood levels, insulin secretion or defects in its function. It has been determined that DM, which can turn from a mild disorder to a serious cause of mortality and morbidity, is associated with chronic inflammation due to innate immune system disorder. The family of large and small, low molecular weight cell signalization proteins that mediate complex interaction are called cytokines. Among these cytokines; interleukins and interferons are found in response to stimuli secreted by leukocytes and various other cells. Cytokines and their receptors show a high affinity for each other. Inflammation resulting from imbalance between pro- and anti-inflammatory cytokines can lead to DM and its complications. Genetic variations in the promoter or intron regions of these cytokines can cause disruption of the balance between cytokines. Thus, gene expression changes can occur with disruption of this balance. An important member of the interleukin-1 (IL-1) super family, which includes pro-inflammatory properties, is interleukin-18 (IL-18) and is produced by various cells. It is thought that IL-18, which is effective in regulating immune response by inducing cytokine gene expression and T helper cell differentiation, may be associated with the development of various diseases such as inflammatory diseases, autoimmune diseases. Genetic variations occurring in the promoter region of the IL-18 gene are associated with the binding of transcription factors and thus can lead to changes in inflammatory cytokine expression or activity. Based on these changes, important information about the pathogenesis of various diseases can be obtained. It is thought that inflammation mediators such as IL-18 may also be effective in the development of DM. Thus, the purpose of this review is; İn addition to giving general information about the complications developing in DM and DM; it is the investigation of the effects of IL-18 gene variations, which are proinflammatory cytokines in the development of microvascular complications of DM, as a genetic risk factor.