The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is "Inflammation" Always Inflammation?

Abstract

Inflammation is a response to infections or tissue injuries. Inflammation was once defined by clinical signs, later by the presence of leukocytes, and nowadays by expression of "proinflammatory" cytokines and chemokines. But leukocytes and cytokines often have rather anti-inflammatory, proregenerative, and homeostatic effects. Is there a need to redefine "inflammation"? In this review, we discuss the functions of "inflammatory" mediators/regulators of the innate immune system that determine tissue environments to fulfill the need of the tissue while regaining homeostasis after injury.

Figure 1

The role of the innate immune system in regaining tissue homeostasis. An injury disturbs the tissue homeostasis and activates the innate immune system leading to the recruitment of several immune cells at the site of injury. These immune cells secrete cytokines, growth factors, and enzymes to establish an inflammatory milieu. They also secrete anti-inflammatory and proregenerative cytokines to promote resolution of inflammation as well as tissue repair. A transient inflammation is often helpful to get rid of the cause of the tissue injury and return to homeostasis. However, an uncontrolled or persistent inflammation promotes tissue remodeling and fibrosis.

Figure 2

Mediators of innate immune system in regaining tissue homeostasis. Innate immune cells secrete several cytokines, growth factors, and enzymes, which promotes either resolution of inflammation and tissue repair/regeneration or tissue remodeling/fibrosis. PTX3: pentraxin 3, ROS: reactive oxygen species, IL: interleukin, TGF: transforming growth factor, MMP: matrix metalloproteinase, TIMP: tissue inhibitor of matrix metalloproteinase, TNF: tumor necrosis factor, MIP: macrophage inhibitory protein, MBP: major basic protein, mMCP: mouse mast cell protease, and PDGF: platelet-derived growth factor.