The crucial roles of inflammatory mediators in inflammation: A review

Abstract

The inflammatory response is a crucial aspect of the tissues' responses to deleterious inflammogens. This complex response involves leukocytes cells such as macrophages, neutrophils, and lymphocytes, also known as inflammatory cells. In response to the inflammatory process, these cells release specialized substances which include vasoactive amines and peptides, eicosanoids, proinflammatory cytokines, and acute-phase proteins, which mediate the inflammatory process by preventing further tissue damage and ultimately resulting in healing and restoration of tissue function. This review discusses the role of the inflammatory cells as well as their by-products in the mediation of inflammatory process. A brief insight into the role of natural anti-inflammatory agents is also discussed. The significance of this study is to explore further and understand the potential mechanism of inflammatory processes to take full advantage of vast and advanced anti-inflammatory therapies. This review aimed to reemphasize the importance on the knowledge of inflammatory processes with the addition of newest and current issues pertaining to this phenomenon.

Keywords: chemokines; cytokines; inflammatory mediators; inflammatory response.

Figure-1

The cyclooxygenase pathway of the arachidonate cascade. In response to chemical and mechanical stimuli, arachidonic acid, a 20-carbon fatty acid with four double bonds (20:4), is released from membrane phospholipids by phospholipase A₂. Prostaglandin endoperoxide H₂ synthase (PGHS) catalyzes the bis-oxygenation of free AA into the unstable endoperoxide PGG₂ and the reduction of PGG₂ into PGH₂, by the coordinated activity of the cyclooxygenase (COX) and the peroxidase domain (POX). PGH₂ is further metabolized by cell-specific terminal isomerases and reductases to yield prostanoids. TXS, thromboxane (Tx) A₂ synthase; PGDS, prostaglandin (PG) D₂ synthase; PGES, prostaglandin (PG) E₂ synthase; PGFS, prostaglandin (PG) F_2a synthase; PGIS, prostaglandin (PG) I₂ synthase. TXA₂ and PGI₂ are unstable metabolites and hydrolyzed within minutes from their synthesis into the inactive metabolites, TxB₂ and 6-keto-PGF_1α (Adapted from[51]).

Figure-2

Macrophage role in inflammation and tissue repair. Upon stimulus, monocytes and resident macrophages activate. They remove tissue debris and produce inflammatory signals that promote the inflammatory response. Macrophages produce a wide array of cytokines, chemokines, and growth factors that promote inflammation, its regulation, and the successful restoration of tissue. They also participate in the regulation of inflammation by removing apoptotic neutrophils, an important process in turning the inflammatory process to one of tissue replacement and remodeling, apoptotic neutrophils that are not removed can undergo necrosis, spilling their toxic content, and perpetuating the inflammatory response (Adapted from [78]).