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Defective immune system response to smallpox vaccine detailed in new study

c dermatitis (as well as samples taken from healthy volunteers without skin disease and from people with another skin condition called psoriasis) to further investigate how dysfunctions in the immune response of people with eczema set the stage for eczema vaccinatum. When exposed to vaccinia virus, the skin samples from healthy volunteers and from those with psoriasis reacted by producing more LL-37. As a result, the replication of the virus was controlled and eventually halted. In contrast, LL-37 production was minimal in skin samples from people with atopic dermatitis and vaccinia replication was poorly controlled. Next, the scientists exposed skin samples from people with atopic dermatitis to vaccinia, and then added LL-37. With the LL-37 supplement, the skin cells successfully controlled the viral replication.

Dr. Leung and his group then looked more closely at why vaccinia infection fails to induce LL-37 production in atopic dermatitis skin. Comparing immune responses of skin cells grown in the lab from healthy volunteers and from people with atopic dermatitis, the researchers found that the latter skin samples produced excessive amounts of IL-4 and IL-13. Adding IL-4 and IL-13 to skin cells from healthy volunteers prior to vaccinia exposure reduced levels of LL-37 production. Conversely, when the scientists applied IL-4- and IL-13-neutralizing antibodies to skin samples from people with atopic dermatitis, LL-37 production increased significantly.

Together, these findings suggest a rationale for new treatment approaches to eczema vaccinatum, notes Dr. Leung. One approach involves developing drugs to mimic the action of LL-37 or developing LL-37-containing creams that could be applied to the skin in order to boost its ability to contain vaccinia virus infection. Another approach could be to develop agents to neutralize IL-4 and IL-13. Although no such drugs are currently marketed, compounds that can neutralize IL-4 and IL-13 are under study as p
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Source:NIH/National Institute of Allergy and Infectious Diseases


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