Kathleen J Smith1, Henry Skelton. 1. Department of Dermatology and Pathology, University of Alabama, Birmingham, Alabama 35294-0009, USA. ksmith@path.uab.edu
Abstract
BACKGROUND: In addition to corticosteroids, there are increasing numbers of anti-inflammatory agents that specifically target bioactive lipids generated from arachidonic acid. Knowledge of the diverse mechanisms of action of these different bioactive lipids holds promise in the therapy of a wide spectrum of cutaneous and systemic disorders. OBJECTIVE: Therapeutic manipulations of these lipid molecules through inhibition, stimulation, or direct replacement have broad physiologic effects. These therapeutic strategies not only modulate inflammation, pain, and hemostatic parameters, they also play a role in cardiac, respiratory, renal, and gastrointestinal function and disease, as well as in angiogenesis and in factors that control cell growth and apoptosis important in carcinogenesis. CONCLUSION: Newer drug discovery methods, including combinatorial chemistry with molecular modeling, have made it possible to develop inhibitors and analogs with increasing specificity and bioactivity and decreasing toxicity. Although the application of these analogs and inhibitors for cutaneous disease is limited today, either as primary agents or adjuvant therapy, these drugs will have a place in our therapeutic regimes of the future. We present a review of the therapeutic agents now available from manipulation of these bioactive lipids, and their role and future in dermatology.
BACKGROUND: In addition to corticosteroids, there are increasing numbers of anti-inflammatory agents that specifically target bioactive lipids generated from arachidonic acid. Knowledge of the diverse mechanisms of action of these different bioactive lipids holds promise in the therapy of a wide spectrum of cutaneous and systemic disorders. OBJECTIVE: Therapeutic manipulations of these lipid molecules through inhibition, stimulation, or direct replacement have broad physiologic effects. These therapeutic strategies not only modulate inflammation, pain, and hemostatic parameters, they also play a role in cardiac, respiratory, renal, and gastrointestinal function and disease, as well as in angiogenesis and in factors that control cell growth and apoptosis important in carcinogenesis. CONCLUSION: Newer drug discovery methods, including combinatorial chemistry with molecular modeling, have made it possible to develop inhibitors and analogs with increasing specificity and bioactivity and decreasing toxicity. Although the application of these analogs and inhibitors for cutaneous disease is limited today, either as primary agents or adjuvant therapy, these drugs will have a place in our therapeutic regimes of the future. We present a review of the therapeutic agents now available from manipulation of these bioactive lipids, and their role and future in dermatology.