E. Corsini et al., ENDOGENOUS INTERLEUKIN-1-ALPHA IS ASSOCIATED WITH SKIN IRRITATION INDUCED BY TRIBUTYLTIN, Toxicology and applied pharmacology, 138(2), 1996, pp. 268-274
Tributyltin (TBT) salts are well-known skin irritants in both human an
d rodents, This study investigated the role of interleukin-1 alpha (IL
-1 alpha) in the process in mice and in murine keratinocytes. The ears
of Balb/c mice were painted with different amounts of TBT (67-536 nmo
l in acetone) or with acetone alone, Two hours later there was dose-re
lated production of IL-1 alpha along with ear swelling and accumulatio
n of skin water, all of which were partially prevented by intraperiton
eal injection of antibody against murine IL-1 alpha. By reverse transc
ription-polymerase chain reaction we were able to show that the neutra
lizing antibody also partially prevented TBT-induced in vivo IL-6 expr
ession but no TBT-induced TNF-alpha expression, suggesting a paracrine
effect of IL-1 alpha on IL-6 production but not TNF-alpha expression
and indicating that other inflammatory mediators are involved, TBT ind
uced both intracellular production of IL-1 alpha and its release into
culture medium in a murine keratinocyte cell line (HEL30). IL-1 alpha
production was inhibited by addition of a neutralizing antibody agains
t IL-1 alpha, which suggests an autocrine effect of IL-1 alpha on its
own production. The intracellular production of IL-1 alpha could be si
gnificantly inhibited by prior treatment with antioxidants, which stro
ngly suggests a role for oxidative species in rite mechanism of action
of TBT in IL-1 alpha induction. The complex-1 inhibitor rotenone also
significantly inhibits IL-1 alpha production. Since TBT causes distur
bances in the respiratory chain in mitochondria, the mechanism of its
action may be the production of reactive oxygen intermediates at the u
biquinone site, which activate transcription factors and promote IL-1
alpha synthesis. (C) 1996 Academic Press, Inc.