The acute inflammatory response is the body's first system of alarm signals that are directed toward containment and elimination of microbial invaders. Uncontrolled inflammation has emerged as a pathophysiologic basis to many of the widely occurring diseases in the general population that were not initially known to be linked to events in the inflammatory response. These include cardiovascular diseases and neurodegenerative diseases (including Alzheimer's disease), and it has now become apparent that inflammation is an important component of cancer progression and the persistence of neuropathic pain. These are diseases that cross many disciplines. To better manage treatment, diagnosis, and prevention of diseases, multidisciplinary research efforts are under way in both academic and industry settings. Since knowledge of the acute inflammatory response in itself spans many disciplines, the editors' mission is to provide in this text an introduction to the cell types, chemical mediators, and general mechanisms that are involved in this primordial first response of the host to invasion. It is also now clear that the termination or the resolution of the acute inflammatory response is an active process, which is pivotal and is the outcome of the acute response. As an endogenous programmed response, the terrain of resolution holds many new possibilities for treatment and prevention of uncontrolled inflammation in a wide range of diseases.

SUMMARY

It is without doubt that resolution of acute inflammation is under strict checkpoint control by endogenous proresolution factors. It is these factors and mechanisms inherent in resolution that are crucial in preventing excessive tissue injury, autoimmunity, and chronic inflammation. In this chapter, resolution and the factors that control it are detailed to underline its importance in human pathology and highlight new and more effective treatment modalities with fewer side effects for chronic inflammatory diseases.

INFLAMMATION IN HEALTH AND DISEASE

Inflammation is a beneficial host response to foreign challenge or tissue injury that leads ultimately to the restoration of tissue structure and function. It is a reaction of the microcirculation that is characterized by the movement of serum proteins and leukocytes from the blood to the extravascular tissue. This movement is regulated by the sequential release of vasoactive and chemotactic mediators, which contribute to the cardinal signs of inflammation – heat, redness, swelling, pain, and loss of tissue function (Figure 2.1A). Local vasodilation increases regional blood flow to the inflamed area and, together with an increase in microvascular permeability, results in the loss of fluid and plasma proteins into the tissues. Concomitantly, there is an upregulation of adhesion molecule expression on endothelial cells and the release of chemotactic factors from the inflamed site, which facilitate the adherence of circulating cells to the vascular endothelium and their migration into the affected area.