Lipid Mediators in Inflammatory Disorders

Abstract

During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.

Increased expression of type 2 3α-hydroxysteroid dehydrogenase/type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma

“…Lipid metabolism including arachidonic acid and PG has been implicated in these disorders (Heller et al 1998). Furthermore, involvement of PPARg has been reported in regulating lipid homeostasis, immune response, cell differentiation and cell proliferation (Heller et al 1998, Bishop-Bailey & Wray 2003, Varley et al 2004.…”

Metabolomics in the Analysis of Inflammatory Diseases

“…Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives (Heller et al, 1998). When investigating inflammation it is important to take into account the many facets of the inflammatory environment that have the potential to play a role in pathology.…”

The Pseudomonas Autoinducer N-(3-Oxododecanoyl) Homoserine Lactone Induces Cyclooxygenase-2 and Prostaglandin E2 Production in Human Lung Fibroblasts: Implications for Inflammation

“…These data support the concept that induction of Cox-2 leads to increased production of PGE 2 . PGE 2 has been shown to cause fever and permeability of vascular endothelium, enhance mucus secretion, and induce pain (20). PGE 2 also synergizes with IL-8 to enhance neutrophil migration (21).…”