Recent in vitro studies document IL-1α and IL-1β secretions upregulated in the cell culture supernatant of human skin equivalents when stimulated with S. scabiei var. canis whole mites (55). Subsequent studies by the same group show unknown components in whole mite extracts of S. scabiei var. canis downregulate secretion of interleukin-1 receptor antagonist (IL-1ra) and IL-8 and stimulate secretion of IL-6 and vascular endothelial cell growth factor (VEGF)

in cultured normal epidermal keratinocytes (56). In the same study see more IL-6, IL-8, granulocyte-colony stimulating factor (G-CSF) and VEGF were upregulated in cultured normal human dermal fibroblasts. Of interest, when keratinocytes were cultured in the presence find more of inflammatory cytokines (IL-1α and IL-1β, TNF-α and IL-17), the same S. scabiei var. canis extract was shown to still downregulate levels of IL-8 secretion and also granulocyte/macrophage-colony

stimulating factor secretion from cultured fibroblasts (57). Furthermore, in this latter study levels of the growth-related oncogene alpha (GROalpha), TGF-α and cutaneous T-cell attracting chemokine from keratinocytes and IL-6 and G-CSF from fibroblasts were also downregulated. Another study using stimulated cultured dermal microvascular endothelial cells documents that the var. canis extract inhibits the 4-Aminobutyrate aminotransferase expression of intracellular adhesion molecule-1 and E-selectin and downregulates secretion of IL-1α (58). Furthermore, these observed inhibitory effects were not altered in the presence of histamine and lipid-derived biologic mediators (59). Over all, these findings confirm uncharacterized mite proteins have immunomodulatory properties that favour invasion of the host by the parasite via down regulating or depressing inflammatory processes of resident cells in the skin and possibly influencing a delayed immune reaction. Interestingly, recent reports describe the proteolytic activity

of house dust mite (HDM) cysteine and serine proteases stimulating human keratinocytes and upregulating IL-8 secretion in vitro (60,61). The specific effects of scabies mite cysteine and serine proteases, homologues of the HDM cysteine protease group 1 and 3 allergens, on keratinocytes still remain to be elucidated (62–64). Similarly, the effect on the skin immune system of other reported scabies mite homologues to HDM allergens is also currently unknown. These include a scabies mite mu class and a delta class glutathione S-transferase group 8 allergen implicated as a major allergen in crusted scabies immune response (65,66), localized to the mite gut (9); and an apolipoprotein, homologous to the C terminus of group 14 allergen (67).