Reduced incidence of insect-bite hypersensitivity in Icelandic horses is associated with a down-regulation of interleukin-4 by interleukin-10 and transforming growth factor-beta1.

The research investigates why Icelandic horses born and exported to Europe as adults are more likely to develop insect bite hypersensitivity (IBH), a form of allergic dermatitis caused by insect bites, than their locally born counterparts. Essentially, these exported horses trigger an interleukin-4 response to insect bites, causing an allergic reaction. However, their European-born progeny have a reduced incidence of IBH, which seems to be due to an interaction of interleukin-10 and transforming growth factor-beta1 down-regulating this reaction.

Understanding the Research

This study’s findings relate to the interplay between the immune response of horses to bites from insects of the genus Culicoides, specifically the production of interleukin-4 (IL-4), and how that may be regulated by both interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1).

• Insects from this genus are not present in Iceland, so Icelandic horses do not develop IBH naturally. However, when Icelandic horses are moved to mainland Europe as adults, they have a greater than or equal to 50% likelihood of developing IBH due to exposure to Culicoides insects.
• Interestingly, the progeny of these exported horses, born in Europe, have a less than 10% incidence of developing IBH. To study this, the researchers compared the immune response of both these groups to the insect allergen, focusing on the blood cells that mediate immune response (PBMCs).
• They found that PBMCs from both groups (IBH-affected and healthy) produced less IL-4, which is commonly associated with allergic response, when stimulated. However, PBMCs from the healthy European-born horses also exhibited down-regulation of IL-4 production, which is associated with a reduced incidence of IBH.
• Further investigation revealed that IL-10 and TGF-beta1, both involved in immune regulation, were crucial in this process. In combination, these two factors seemed to reduce the proportion of cells producing IL-4 and the production of IL-4 itself in stimulated PBMC cultures from the first-generation, IBH-affected horses.
• The study found this effect could not be replicated with either factor alone, suggesting that both IL-10 and TGF-beta1 are required for down-regulation. Conversely, the production of IL-4 was increased when IL-10 and TGF-beta1 were inhibited.
• This interplay between IL-10, TGF-beta1 and IL-4 is present in horses for the first time, suggesting a regulatory mechanism governing allergic reaction. The research suggests that in horses, IL-10 and TGF-beta1 play a role in the down-regulation of IL-4-induced, allergen-specific Th2 cells, leading to a reduction in IBH incidence.