Dedication I would like to dedicate this work to my husband, Stephen Nadworny; my sister and her husband, Celeste and Brent Adrian; and my parents, Ross and Coleen Taylor. They have been a huge support to me. Abstract Although nanocrystalline silver is used commercially to treat burns and wounds, the mechanisms of action (MOA) for its activity are not clear. The purposes of this work were to determine if nanocrystalline silver has antiinflammatory activity, determine physicochemical properties

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... ritical for its MOA, and develop nanocrystalline silver-derived solutions for use in the treatment of lung diseases, including ARDS and pneumonia. In a porcine contact dermatitis model, nanocrystalline silver had anti-inflammatory activity independent of antimicrobial activity, with increased apoptosis induction in inflammatory cells, but not keratinocytes; decreased expression of TNF-α, TGF-β, IL-8, and MMPs; and increased expression of IL-4, EGF, KGF, and KGF-2. Treatment with AgNO 3 (Ag + ) increased inflammation, and caused apoptosis induction in keratinocytes. Thus, nanocrystalline silver releases additional species, perhaps Ag (0) -containing clusters, resulting in anti-inflammatory activity. SIMS analysis showed significant deposition of Ag-clusters after nanocrystalline silver, but not AgNO 3 , treatment. Nanocrystalline silver had a systemic effect, despite SIMS analysis showing minimal skin penetration by silver, suggesting that nanocrystalline silver interacts with cells near tissue surfaces that release signals altering the inflammatory cascade. Relative to various Ag + -releasing dressings, nanocrystalline silver had significantly enhanced antimicrobial activity, Ag +resistant bacteria kill, and was not prone to development of resistant bacteria, indicating that nanocrystalline silver releases antimicrobial species additional to Ag + , and has multiple bactericidal MOA. Single silver nanocrystals are inactive,