Rw. Lange et al., ANTIOXIDANTS ATTENUATE ANTHRALIN-INDUCED SKIN INFLAMMATION IN BALB C MICE - ROLE OF SPECIFIC PROINFLAMMATORY CYTOKINES/, Journal of leukocyte biology, 64(2), 1998, pp. 170-176
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.