Intranasal administration of protein antigen is an efficient way to in
duce mucosal tolerance. Suppressive mechanisms that might be involved
in this phenomenon include down-regulation of T-helper type-1 (Th1)-me
diated processes by Th2 cells. However, since Th2 responses can also b
e subjected to mucosal tolerance, we wanted to investigate whether sup
pression of a typical Th1 response, such as a delayed-type hypersensit
ivity (DTH) reaction by intranasal tolerance induction, was causally r
elated to up-regulation of Th2 responses. We therefore treated mice ei
ther systemically or locally with anti-interleukin-4 (IL-4) or anti-IL
-10 antibodies before intranasal tolerance induction or before sensiti
zation for DTH to see whether we could prevent or abrogate tolerance.
Although the up-regulation of antigen-specific IgE levels in tolerant
mice could be prevented by anti-IL-4 treatment, the extent of toleranc
e as measured by suppression of DTH was not affected. We therefore con
clude that up-regulation of Th2 responses observed after intranasal to
lerance induction is an additional or consequential rather than a nece
ssary reaction.