PRODUCTION OF IL-1-ALPHA AND IL-1-BETA BY HUMAN SKIN EQUIVALENTS PARASITIZED BY SARCOPTES-SCABIEI

Human skin equivalents (HSEs) were used as a model to investigate inte rleukin (IL)-1 alpha and IL-1 beta secretions by keratinocytes stimula ted by Sarcoptes scabiei (SS). SS mites burrowed into the stratum corn eum when placed on the surface of cultured HSEs. Mites lived for 14 da ys. Mites and mite products induced cells in the HSEs to secrete IL-1 alpha and IL-1 beta within 16 hr. Scabies mites induced production of greater amounts of IL-1 alpha than IL-1 beta. Hepatocyte growth factor in the culture medium at 3 and 30 ng/ml upregulated the secretions of both IL-1 alpha and IL-1 beta by mite-infested skin equivalents, wher eas 10 ng/ml of IL-6 upregulated production of only IL-1 beta. Therefo re, these cytokines were important immunomodulating factors influencin g keratinocyte secretion of IL-1 alpha and IL-1 beta in vitro. The res ults of this study provide the first evidence that keratinocytes (poss ibly fibroblasts) in the skin produce these cytokines in response to s cabies mites or other ectoparasitic arthropods. Because IL-1 alpha and IL-1 beta are potent inducers of inflammation and keratinocytes are a mong the first effector cells to encounter scabies mites and their pro ducts, these cells may be key initiators of the inflammatory/immune re action to scabies.