Inflammation-a Critical Appreciation of the Role of Myeloid Cells

Abstract

What is inflammation's big idea? In this brief overview of the role of myeloid cells in inflammation, we will critically discuss what drives the initiation, amplification, and resolution of inflammation in different anatomical sites in response to different pathological stimuli. It can be argued that we have a good understanding of the basic principles that underlie myeloid cell activation and the mobilization of innate immune cells to sites of injury and infection in acute inflammation. The challenge now for inflammation biologists is to understand how resolution of this normal physiological response goes wrong in hyperacute and chronic inflammation. A better understanding of how inflammation is regulated will allow us to develop new anti-inflammatory drugs that will reduce the burden of inflammatory disease without compromising the patient's immune defenses against infectious disease. Ideally such drugs should encourage a return to homeostasis and enhance tissue repair processes.

Figure 1. Time course of a typical acute inflammatory response

A schematic representation of the ideal outcome of an acute inflammatory response, i.e. resolution, is shown as a dashed line. Two potential outcomes leading to significant clinical sequelae are shown, hyper-acute inflammation e.g. septic shock and non-resolving, chronic inflammation e.g. rheumatoid arthritis.

Figure 2. The inflammatory set point hypothesis

This schematic representation highlights the balance between locally produced pro-inflammatory and endogenous anti-inflammatory / pro-resolution mediators in determining the magnitude of the inflammatory response in response to a given stimulus.

Figure 3. Inflamm-aging, do inflammatory response change with age?

This schematic representation compares the ‘normal’ inflammatory response (solid line) with the inflammatory response seen in aged populations (dashed line). Aged populations show increased basal levels of systemic inflammation and may show differences in the magnitude of the response to inflammatory stimuli and/or altered resolution.