Role of Bioactive Lipids in Chronic Inflammation

Abstract

Inflammation is the pathophysiological process in which there is defensive response occur in the host to the tissue injury and invasion of microorganism. Acute inflammation usually self- limiting, when it fails to resolve that leads to chronic inflammation. Lipids are considered as important regulatory factors of inflammation. Various lipid mediators such as leukotriene, prostaglandins and other bioactive lipids are connected in various inflammatory disorders. They are formed mainly by the cells involved in inflammatory processes and engaged in the inflammatory mechanisms. The objective of this article is to summarize the involvement of bioactive lipids in chronic inflammation. Information included in this article taken from past literature reviews. Bioactive lipids are the widest family plays important role in chronic inflammation. They are considered as initiators of inflammation. Prostaglandins and eicosanoids are involved in the process. Prostaglandins are especially PGE2 and PGI2 act as cytokine amplifiers causes transition to chronic inflammation. These occurs by five major mechanisms such as pro inflammatory cytokine release cascade, amplification of innate immune response, activation of T helper cells, recruitment of chronic inflammatory cells and increase of pro inflammatory genes induced by cytokines. There are linkage between prostaglandin related genes and susceptibility to several chronic diseases such as crohn's disease, asthma and multiple sclerosis suggested by several articles. On the other hand, leukotrienes are connected to the pathogenesis of atherosclerosis, inflammatory bowel diseases, psoriasis, rheumatoid arthritis, also in asthma and multiple sclerosis. In case of lysophospholipids and sphingolipids they are asymmetrically distributed in plasma membrane and have great molecular diversity as they have molecular linkage with other molecules such as ethanolamines, choline, inositol, serine and fatty acids such as phosphoinositides, lysoglycerophospholipids and ceramides. Biochemical inter-conversion can occur in between them and with also others bioactive lipids. Sustained activation of most biologically active lysophospholipids are related with several chronic inflammatory diseases including obesity, diabetes, cancer, atherosclerosis and rheumatoid arthritis. If we consider, sphingolipids they are mostly associated with immune dependent and vascular chronic diseases such as diabetes, chronic obstructive pulmonary disease, inflammatory bowel diseases, neuro-inflammatory disorders. Such as, in diabetes there is adipose tissue inflammation occur and insulin resistance developed which is caused by excessive signaling of ceramides which is a sphingolipid. Also, ceramide and its metabolites are play role in regulation of vascular integrity and function. If there is any alterations of these lipids vascular dysfunction occur which is associated with chronic inflammation. In chronic inflammation, bioactive lipids and their metabolites and signaling are dysregulated. If the endogenous mechanisms involved in this dysregulation or modulation of homeostatic process can be managed rather than suppressing inflammation it can be beneficial for the therapeutic management of the disease in future.