ANTIOXIDANTS ATTENUATE ANTHRALIN-INDUCED SKIN INFLAMMATION IN BALB C MICE - ROLE OF SPECIFIC PROINFLAMMATORY CYTOKINES/

Anthralin is the most common therapeutic agent among a small number of pro-oxidant, 9-anthrones effective in the topical treatment of psoria sis, However, the usefulness of this drug is diminished by toxic side effects, including skin irritation and inflammation. The activities of anthralin are believed to be mediated by the generation of reactive o xygen intermediates and anthrone radicals produced in the skin, in thi s study, the dermal inflammatory response to anthralin was determined using a mouse ear swelling test. Maximum ear swelling induced by anthr alin coincided with the elevation of cytokine mRNA expression in the s kin, including interleukin-6, granulocyte-macrophage colony-stimulatin g factor, macrophage inflammatory protein-2, and tumor necrosis factor alpha at 24 h post challenge, The role of free radical generation in ear swelling and cytokine modulation were examined by systemic adminis tration of cell permeable and impermeable antioxidants before anthrali n challenge, Superoxide dismutase and alpha-tocopherol acetate, but no t the glutathione precursor N-acetyl cysteine, were effective inhibito rs of anthralin-induced ear swelling and cytokine elevation, Maximum i nflammatory cell infiltration occurred 72-96 h post anthralin challeng e and Tvas also reduced by antioxidants. These data suggest that oxida tive stress, generated at the site of anthralin treatment, alters the expression of dermal chemokines and other cytokines resulting in the r ecruitment of inflammatory cells, Systemic antioxidant administration may provide opportunities for therapeutic intervention against anthral in-associated toxicities.