LETTER
Treatment of Behcet Disease with Pentoxifylline
Jedd D. Wolchok, MD, PhD
15 March 1997 | Volume 126 Issue 6 | Page 493
TO THE EDITOR:
Yasui and colleagues [1] recently published an interesting report on the efficacy of pentoxifylline in the treatment of three patients with Behcet disease. The precise cause of Behcet disease remains unknown; however, international diagnostic criteria include the classic symptoms of oral and genital ulcerations, uveitis, and skin lesions [2].
I was intrigued by one possible mechanism of action of pentoxifylline that may help elucidate the cause of Behcet disease. This compound, a methylxanthine derivative, has been shown to inhibit the production of various proinflammatory cytokines, especially tumor necrosis factor-
(TNF-) [3]. Interestingly, levels of TNF- induced by lipopolysaccharide have been shown to be increased in peripheral blood mononuclear cells from patients with Behcet disease when compared with levels in age-matched healthy controls [4]. Thus, TNF- may play a substantial role in the pathogenesis of Behcet disease, either directly or through the induction of other cytokines. This proposed mechanism is supported by the finding that thalidomide, an inhibitor of TNF- action, also reduces mucosal ulcerations in patients with Behcet disease [2].
Yasui and colleagues reported increased baseline neutrophil chemotaxis and superoxide production in patients with Behcet disease. These variables returned to normal after initiation of pentoxifylline treatment. This finding may be partly explained by a TNF--mediated increase in the production of interleukin-8, a potent activator of neutrophils [5]. It would be of interest to know whether pentoxifylline had any effect on TNF- production in the authors' three patients. As the authors propose, a formal placebo-controlled clinical trial of pentoxifylline for Behcet disease should be done.
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Author and Article Information
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Memorial Sloan-Kettering Cancer Center, New York, NY 10021
1. Yasui K, Ohta K, Kobayashi M, Aizawa T, Komiyama A. Successful treatment of Behcet disease with pentoxifylline. Ann Intern Med. 1996; 124:891-3.
2. Schumacher HR Jr, ed. Primer on Rheumatic Diseases. 10th ed. Atlanta: Arthritis Foundation; 1993:206-7.
3. Nakamura S, Sugita M, Tanaka S, Ohno S. Enhanced production of in vitro tumor necrosis factor- from monocytes in Behcet's disease. Acta Soc Ophthalmol Jap. 1992; 96:1282-5.
4. Neuner P, Klosner G, Schauer E, Pourmojib M, Macheiner W, Grunwald C, et al. Pentoxifylline in vivo down-regulates the release of IL-1 ß, IL-6, IL-8 and tumour necrosis factor- by human peripheral blood mononuclear cells. Immunology. 1994; 83:262-7.
5. Lee TH, Lee GW, Ziff EB, Vilcek T. Isolation and characterization of eight tumor necrosis factor-induced gene sequences from human fibroblasts. Mol Cell Biol. 1990; 10:1982-8.
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