Cytokines and chemokines
- Transforming growth factor.
- Tumor necrosis factor.
- The effects of TNF-? on wound healing.
- Chimeric mouse antihuman IgG1 monoclonal antibodies.
Cytokines are soluble low-molecular weight glycoproteins or small polypeptides that act in an autocrine or paracrine manner between leukocytes and other cells. Cytokines have many biologic functions and are important for leukocyte growth and differentiation as well as activation and migration. Cytokines orchestrate defense, growth, fibrosis, angiogenesis, inflammation, and neoplasm control. They are synthesized by immunologic cells such as lymphocytes and monocytes/macrophages and by nonimmunologic cells such as keratinocytes and endothelial cells. Proinflammatory cytokines include interleukin-1 (IL-1), IL-2, interferon-? (IFN-?), and tumor necrosis factor-? (TNF-?), and antiinflammatory cytokines include IL-1 receptor antagonist, IL-4, IL-10, and transforming growth factor-? (TGF-?)4,5. The overexpression of inflammatory cytokines or decreased levels of antiinflammatory cytokines can lead to inflammatory cutaneous disorders. The CD4+ T-helper (Th) lymphocyte paradigm has also contributed to our understanding of inflammatory cutaneous disorders. CD4+ Th1 cells evoke cell-mediated immunity and phagocyte-dependent inflammation, while CD4+ Th2 cells evoke strong antibody, or humeral, immune responses, including those of the immunoglobulin E (IgE) antibody class, and inhibit phagocytosis.
[...] As our current knowledge of the immune system continues to grow, the application of safe and efficacious immunomodulators to treat these common skin conditions will continue to change and shape the field of dermatology. Conclusion Cytokines and chemokines are critical messengers of the immune system, as well as the homeostasis of peripheral tissues such as the skin. This class of molecules has been implicated in the pathogenesis of a number of dermatologic diseases. SUMMARY There has been a radical increase in our understanding of the pathogenesis of wound healing, scarring, skin cancer, and inflammatory dermatoses as well as improvements in their management and treatment. However, effective cures for these dermatologic conditions remain [...]
[...] When activated, these kinases phosphorylate cytoplasmic signal transduction proteins that bind to cis- acting elements and subsequently regulate cellular gene transcription rates. Fibroblast proliferation as well as collagen, fibronectin, and glycosaminoglycan production are decreased when IFNs bind to their receptors on fibroblasts. Interferon-? activates dermal fibroblast synthesis of collagenase and reduces the production of its natural inhibitor, tissue inhibitor of metalloproteinase-I (TIMP-I). In contrast, IFN-? has been shown to inhibit collagen production. Interferon-? inhibits fibroblast proliferation, chemotaxis, and production of ECM macromolecules, including collagen and glycosaminoglycans. [...]