Itching to Understand: Horses and Insect Bite Hypersensitivity

Insect bite hypersensitivity (IBH)—an allergic reaction to salivary gland proteins from Culicoides midges—is one of the most common skin diseases diagnosed in horses. In an effort to identify a novel, effective treatment, researchers recently looked at the role of skin cells in IBH.

“We know that IBH is a complex allergic condition, a type-1 hypersensitivity that involves activation of T helper type-2 cells (Th2) as well as the action of specific cytokines, such as interleukins 4, 5, and 13,” explained Kathleen Crandell, Ph.D., a nutritionist for Kentucky Equine Research.

Recent research in human medicine showed that the skin cells themselves, the keratinocytes, may also play be involved in the development of type-1 hypersensitivities.

To better understand the role of keratinocytes in IBH, skin cells from healthy and IBH-affected horses were cultured in the laboratory. Those keratinocytes were stimulated with (1) Culicoides allergens and (2) an allergen cytokine milieu. This milieu was composed of various cytokines designed to mimic the milieu produced by Th2 cells. After stimulation with these two allergen mixtures, keratinocyte transcripts were measured. Transcripts give information on the different types of proteins, such as cytokines, being produced by the keratinocytes after stimulation.

Researchers identified no change in transcripts after stimulating keratinocytes with known Culicoides allergens. However, when the keratinocytes were stimulated with the allergen cytokine milieu, the transcripts for many pro-inflammatory cytokines were upregulated. This included interleukin-31, which is often dubbed the “itchy” cytokine. Transcripts were upregulated in keratinocytes from both healthy and IBH-affected horses.

“This is the first time that researchers have demonstrated that equine keratinocytes are capable of producing the cytokine IL-31. These data also suggest that IL-31 is a key player in the pathogenesis of IBH,” Crandell said.

Overall, this research suggests that keratinocytes may act as amplifiers of the allergic immune reaction. Further research in this field will yield additional information on the pathways involved in IBH. A more complete picture of IBH will then hopefully identify potential targets for novel therapeutic drugs.

“Currently, IBH is treated symptomatically with corticosteroids to decrease inflammation and anti-histamines. Omega-3 fatty acids, particularly DHA and EPA, decrease inflammation and hypersensitivity, and improve the overall health of the skin,” Crandell remarked.

 ^*Cvitas, I., S. Oberhaensli, and T. Leeb. 2022. Equine keratinocytes in the pathogenesis of insect bite hypersensitivity: Just another brick in the wall? PLoS One 17(8):e0266263.