Recent evidence suggests that a deficiency in one o
r mo
re hepatop
rotective
regulato
ry mechanismsmay cont
ribute to dete
rmining susceptibility in d
rug-induced live
r disease. In the p
resent study, weinvestigated the
role of inte
rleukin (IL)-13 in acetaminophen (APAP)-induced live
r disease (AILD).Following APAP (200 mg/kg) administ
ration to male C57BL/6 wild-type (WT) mice, hepatotoxicitydeveloped up to 24 h post-APAP, with a concomitant inc
rease in se
rum IL-13 concent
ration. P
ret
reatmentof these mice with an IL-13-neut
ralizing antibody exace
rbated live
r inju
ry, as did APAP administ
rationto IL-13 knockout (KO) mice in compa
rison to WT mice. No diffe
rence was obse
rved in eithe
r ove
rallAPAP-p
rotein adduct fo
rmation o
r live
r glutathione levels between KO
and WT mice following APAPadminist
ration, suggesting that the inc
reased susceptibility of IL-13 KO mice to AILD was not due toenhanced APAP bioactivation but
rathe
r inju
rious downst
ream events. In this
rega
rd, multiplex antibodya
rrays we
re used to identify potential IL-13-
regulated bioma
rke
rs, including va
rious cytokines
andchemokines, as well as nit
ric oxide (NO), associated with AILD that we
re p
resent at highe
r concent
rationsin the se
ra of APAP-t
reated IL-13 KO mice than in WT mice. Subsequent inhibition studies dete
rminedinte
rfe
ron-
![](/images/gifcha<font color=)
rs/gamma.gif" BORDER=0 >, NO, neut
rophils, natu
ral kille
r cells,
and natu
ral kille
r cells with T-cell
recepto
rs hadpathologic
roles in AILD in IL-13 KO mice. Taken togethe
r, these
results suggest that IL-13 is a c
riticalhepatop
rotective facto
r modulating the susceptibility to AILD
and may p
rovide hepatop
rotection, in pa
rt,by down-
regulating p
rotoxicant facto
rs
and cells associated with the innate immune system.