Targeting tumor necrosis factor alpha. New drugs used to modulate inflammatory diseases.
Since its discovery, the understanding of the roles for TNF-alpha in human biology and disease has grown. Receptors for TNF are found on virtually all cell types, and many physiologic processes seem to be altered by TNF-alpha. The understanding of how TNF-alpha is involved in the pathophysiology of diseases, such as inflammatory diseases, has allowed the development of new drugs that can interfere with excess TNF-alpha and thus has allowed novel therapies for rheumatoid arthritis and Crohn's disease. As the role of TNF-alpha in other diseases becomes better understood, such TNF-alpha-modulating drugs may find further applications. In the skin, TNF-alpha is prominent cytokine that seems to be important in allergic and irritant contact dermatitis and inflammatory skin conditions. Modulating TNF-alpha activity in the skin may provide therapeutic benefits for a variety of skin conditions (Table 4). Tumor necrosis factor-alpha levels are elevated in skin lesions of psoriasis. A few reports have already suggested that etanercept and infliximab may offer a therapeutic effect in patients with psoriasis. Clinical studies evaluating the true efficacy of these drugs in psoriasis are under way. Specifically, the authors and others are involved in a double-blind, placebo-controlled study to assess the efficacy of etanercept for psoriasis. Thalidomide has been used off-label with some success to treat a number of dermatologic diseases, including several inflammatory skin conditions. Etanercept and infliximab might perhaps prove efficacious for inflammatory skin conditions as well. Finally, it is possible that drugs targeting TNF-alpha may have yet-unrecognized serious side effects. Because TNF-alpha seems to be a central cytokine in UVR-induced apoptosis, the chronic use of TNF-alpha-altering drugs might increase the risk for skin cancers. Tumor necrosis factor-alpha also plays some role in cutaneous wound healing; the effect these drugs might have on this process is also unknown at this time. Certainly, much is already [table: see text] known about TNF-alpha and how it plays many central roles. This understanding has allowed the development of useful new drugs for intractable disease. As the understanding of TNF-alpha and other cytokine biology increases, so will the number of potential therapeutic agents.
LaDuca
J R
JR
Department of Dermatology, University of Rochester School of Medicine, Rochester, New York, USA.
Gaspari
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000627:therapeutic use; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000502:physiology; D000069285:Infliximab; D011565:Psoriasis / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012867:Skin / Q000503:physiopathology; D012871:Skin Diseases / Q000188:drug therapy* / Q000503:physiopathology; D013792:Thalidomide / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D003879:Dermatologic Agents; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D000069285:Infliximab; D000068800:Etanercept