General Medical Information

Cytokines (Growth Factors) In Wound Healing

David J. Terris

Cytokines are polypeptide signal proteins that are released from local tissues or blood components and are instrumental in modulating cellular functions, including cell proliferation, differentiation, tissue regeneration, and wound healing. Unfortunately, understanding the complex interactions involved with the various cytokines is made even more difficult because of the confusing nomenclature. Specifically, some cytokines are named for their cell of origin (e.g., platelet-derived growth factor [PDGF]), whereas others are named for their target cell (e.g., epidermal growth factor [EGF]). This occurred in some cases because the factors were named before the major activities were known. In addition, some cytokines are named for their first reported action (e.g., transforming growth factor-b). Finally, the actions of cytokines may be complex and numerous and unable to be described by a single name.

The mechanism of action of the cytokines may be through endocrine (secreted by one population of cells and having distant effects), autocrine (secreted by cells which then are themselves modulated by the factor), or paracrine (secreted by cells and affecting neighboring cell populations) activity. Each cytokine binds specific cell surface receptors, which in turn modulate the activities of second messengers (such as intracellular cAMP).

The cytokines can be divided into two major categories: angiogenic growth factors and bone morphogenetic proteins. There are four major families of angiogenic growth factors: transforming growth factor, EGF, PDGF, and fibroblast growth factor (FGF). . Although the only U.S. Food and Drug Administration-approved application of cytokines is the use of PDGF for diabetic ulcers, the wealth of experimental evidence regarding the value of growth factors in wound healing has brought the field to the brink of widespread clinical applicability, and some of this progress is indicated below.