Abstract

ASSOCIATION OF INTERLEUKIN 1 LEVEL WITH THE SEVERITY OF AORTIC VAVLE STENOSIS IN DIABETIC PATIENTS 2019

Abdul Hussein Razzaq Ali*, Mohammed Sharem Mahbool and Ghalib Kadhem Maan

ABSTRACT

Interleukin-1 (IL-1) proteins are members of the small-secreted proteins family and have a broad range of prominent roles in the immune response (Gibson et al., 2014). This family belongs to a wider family of ligands, which to date, contains 11 conserved members (originally named IL-1 F1-F11): IL-1α, IL-1β, IL-18, IL-33, IL-36a, IL-36b, IL-36g, IL-1RN, IL-36Ra, IL-38 and IL-37. IL-1 members are encoded by the IL-1 gene cluster at chromosomal band 2q14 (Vandenbroeck, 2006). IL-1 proteins (approximately 8–80 kDa) have specific effects on the interactions and communication between cells and f referred as cytokines. Cytokines may act on the cells that secrete them (autocrine action), on adjacent cells (paracrine action), or in on distant cells (endocrine action). Cytokines can be divided into several classes, including lymphokines, monokines, chemokines and interleukins. The IL-1-family of cytokines, and IL-1 signalling, is involved in many physiological processes in mammals, including regulation of homeostasis and metabolism, stress signalling and tissue regeneration and repair, in addition to regulation of infectious immunity and chronic sterile inflammatory processes. Sterile inflammation refers to activation of the immune system, which is not associated with pathogen invasion. The term IL-1 generally encompasses two related agonistic (activating) cytokines, interleukin-1 alpha (IL-1α) and interleukin-1beta (IL-1β), which are encoded by two separate genes. IL-1α was the first interleukin to be identified and was found to affect several types of cells and organs at low concentration (Vandenbroeck, 2006). The IL1-α coding region is located in close proximity to the IL1-β gene, and both gene products exhibit agonistic effects, activating the IL-1 receptor (IL-1R). They are located downstream to an interleukin-1 receptor antagonist (IL-1Ra) encoded by the IL-1RN gene. In addition, this cluster also contains the genes encoding IL-1 receptors type 1 and 2, IL1RI (80 kDa) and IL1RII (60–68 kDa) (Walley et al., 2004). IL-1 signalling is regulated by its own family members, acting as modulators of the inflammation response. In this article, we will describe the basic functions and biology of IL-1 α and β and their natural inhibitors (e.g. antagonists), how these molecules are synthesised and processed, and some aspects of the receptors to which they bind. Aortic stenosis and diabetes mellitus are both progressive diseases which, if left untreated, result in significant morbidity and mortality. There is evidence that the prevalence of diabetes is substantially increased in patients with aortic stenosis and those with diabetes have increased rates of progression from mild to severe aortic stenosis. There are good data supporting the hypothesis that aortic stenosis and diabetes mellitus are associated with diabetes mellitus being detrimental towards the quality of life and survival of patients. Thus, a thorough understanding of the pathogenesis of both of these disease processes and the relationship between them aids in designing appropriate preventive and therapeutic approaches. This review aims to give a comprehensive and up-to-date insight into the influence of diabetes mellitus on patients with degenerative aortic stenosis, as well as the prognosis and therapeutic approach to these patients.

Keywords: Aortic stenosis, diabetes mellitus, atherosclerosis, prognosis, Interleukin-1 (IL-1).