Influence of taurine and a substituted taurine on the respiratory burst pathway in the inflammatory response.

Introduction Psoriasis is a common skin disease and provides a useful model to study the pathogenic significance of chemical mediators of inflammation both in vivo and in vitro. The histological features of this condition include increase epidermal cell proliferation and infiltration of neutrophils, macrophages and lymphocytes into the lesions. In fact, neutrophil infiltrates have been reported to be one of the earliest phenomena in pre-pinpoint lesions [ 11. Elevated levels of leukotriene B, (LTB,) have been reported in extracts of psoriatic skin lesions [Z], suggesting a pathogenic role for this chemoattractant lipoxygenase product. On the other hand, prostaglandin E, (PGE,) levels in psoriatic skin lesions do not differ significantly from clinically uninvolved skin [3] and are not believed to play a significant pro-inflammatory role in psoriasis. Support for a pathogenic role of LTB, derives in part from studies demonstrating that benoxaprofen, a 5-lipoxygenase (E.C. 1.1 3.1 1.12) inhibitor, causes marked improvement in patients with severe psoriasis [4]. Conversely, specific cyclo-oxygenase (E.C. 1.14.99.1) inhibitors, such as indomethacin, may stimulate the lipoxygenase pathway by diversion of substrate and have been reported to exacerbate the condition [S]. The generation of all arachidonic acid-derived products is inhibited by corticosteroids, which are phospholipase A, inhibitors. However, these drugs have undesirable sideeffects which limit their use. Therefore, the development of non-toxic anti-psoriatic drugs would provide new therapeutic approaches to this disease. Activation of oxidative metabolism in leucocytes leads to generation of reactive oxidants (RO) in a process designated the respiratory burst [6, 71. Such production of RO is believed to play a role in the pathogenesis of inflammatory diseases by causing ‘auto-oxidative damage’ at the site of inflammation [ 81. Hydrogen peroxide (H202) produced during the respiratory burst is detoxified by catalase