Anthralin is the most common therapeutic agent among a small number of
pro-oxidant, 9-anthrones effective in the topical treatment of
psoriasis. 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 oxygen intermediates and
anthrone radicals produced in the skin. In this study, the dermal inflammatory response to
anthralin was determined using a mouse ear swelling test. Maximum ear swelling induced by
anthralin coincided with the elevation of
cytokine mRNA expression in the skin, including
interleukin-6,
granulocyte-macrophage colony-stimulating 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 administration of cell permeable and impermeable
antioxidants before
anthralin challenge.
Superoxide dismutase and
alpha-tocopherol acetate, but not the
glutathione precursor N-acetyl
cysteine, were effective inhibitors of
anthralin-induced ear swelling and
cytokine elevation. Maximum inflammatory cell infiltration occurred 72-96 h post
anthralin challenge and was also reduced by
antioxidants. These data suggest that oxidative stress, generated at the site of
anthralin treatment, alters the expression of dermal
chemokines and other
cytokines resulting in the recruitment of inflammatory cells. Systemic
antioxidant administration may provide opportunities for therapeutic intervention against
anthralin-associated toxicities.