Insect bite hypersensitivity (IBH) is an allergic
dermatitis of horses caused by
IgE-mediated reactions to
bites of insects of the genus Culicoides. IBH does not occur in Iceland due to the absence of Culicoides. However, Icelandic horses exported to mainland Europe as adults (1st generation) have a > or =50% incidence of developing IBH. In contrast, their progeny (2nd generation) has
a <10% incidence of IBH. Here we show that peripheral blood mononuclear cells (PBMC) from Icelandic horses born in mainland Europe and belonging either to the IBH or healthy subgroup produce less
interleukin (IL)-4 after polyclonal or
allergen-specific stimulation when compared with counterparts from horses born in Iceland. We examined a role of
IL-10 and
transforming growth factor (TGF)-beta1 in down-regulation of
IL-4 in healthy 2nd generation Icelandic horses. Supernatants of PBMC from 2nd generation healthy horses down-regulated the proportion of IL-4-producing cells and
IL-4 production in stimulated cultures of PBMC from 1st generation IBH. This inhibition was mimicked by a combination of
IL-10 and
TGF-beta1 but not by the single
cytokines. Cultures of stimulated PBMC of healthy 2nd generation horses produced a low level of
IL-4, but
IL-4 production was increased by anti-equine
IL-10 and anti-human
TGF-beta1. This shows for the first time that in horses,
IL-10 and
TGF-beta1 combined regulate
IL-4 production in vitro. It is suggested that in this naturally occurring
IgE-mediated
allergy,
IL-10 and
TGF-beta1 have a role in the down-regulation of IL-4-induced
allergen-specific Th2 cells, thereby reducing the incidence of IBH.