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  • Human serum-derived alpha-1 proteinase inhibitor (alpha-1-antitrypsin or AAT) with immunomodulating and anti-inflammatory activity. Upon administration, AAT reduces the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-32, IL-6, and proteinase 3, and induces the production of anti-inflammatory cytokines, such as IL-10 and the IL-1 receptor antagonist IL-1RN. This agent also downregulates heparan sulfate and reduces the expansion of cytotoxic effector T cells, interferes with the maturation of dendritic cells and increases T regulatory cells. Altogether, AAT may attenuate acute graft-versus-host disease (GvHD) and may facilitate graft acceptance and survival. In addition, AAT enhances levels of cAMP and activation of cAMP-dependent protein kinase A. AAT, a 52kD protein and serine protease inhibitor, belongs to the serpin superfamily. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C82258\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C82258\' NCI Thesaurus)
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