OBJECTIVE: Interleukin 1-beta (IL-1beta) is a major inflammatory cytokine. Blockade of the IL-1beta pathway is therapeutically efficacious in type 2 diabetes, but the mechanistic effects on the immune system are incompletely understood. RESEARCH DESIGN: We administered an IL-1 receptor antagonist, anakinra, to 7 type 1 diabetes patients in order to investigate the immunologic and metabolic effects of this drug. Mechanistic assays were performed before and after drug administration. RESULTS: A novel signature was observed, with reduced serum interleukin 8 (IL-8) levels and reduced CD11b integrin expression on monocytes associated with increased CXCR1 expression. CONCLUSIONS: This set of linked phenotypes suggests that blockade of the IL-1beta pathway results in the reduced ability of mononuclear cells to traffic to sites of inflammation. Mechanistic studies from large scale trials using IL-1 blockade in type 1 diabetes should focus on changes in monocyte trafficking and the IL-8 pathway.
OBJECTIVE:Interleukin 1-beta (IL-1beta) is a major inflammatory cytokine. Blockade of the IL-1beta pathway is therapeutically efficacious in type 2 diabetes, but the mechanistic effects on the immune system are incompletely understood. RESEARCH DESIGN: We administered an IL-1 receptor antagonist, anakinra, to 7 type 1 diabetespatients in order to investigate the immunologic and metabolic effects of this drug. Mechanistic assays were performed before and after drug administration. RESULTS: A novel signature was observed, with reduced serum interleukin 8 (IL-8) levels and reduced CD11b integrin expression on monocytes associated with increased CXCR1 expression. CONCLUSIONS: This set of linked phenotypes suggests that blockade of the IL-1beta pathway results in the reduced ability of mononuclear cells to traffic to sites of inflammation. Mechanistic studies from large scale trials using IL-1 blockade in type 1 diabetes should focus on changes in monocyte trafficking and the IL-8 pathway.
Authors: Yujuan Zhang; Saloni Gupta; Alexandra Ilstad-Minnihan; Sashi Ayyangar; Arielle D Hay; Virginia Pascual; Norman T Ilowite; Claudia Macaubas; Elizabeth D Mellins Journal: Clin Immunol Date: 2018-06-19 Impact factor: 3.969
Authors: Antoinette Moran; Brian Bundy; Dorothy J Becker; Linda A DiMeglio; Stephen E Gitelman; Robin Goland; Carla J Greenbaum; Kevan C Herold; Jennifer B Marks; Philip Raskin; Srinath Sanda; Desmond Schatz; Diane K Wherrett; Darrell M Wilson; Jeffrey P Krischer; Jay S Skyler; Linda Pickersgill; Eelco de Koning; Anette-G Ziegler; Bernhard Böehm; Klaus Badenhoop; Nanette Schloot; Jens Friis Bak; Paolo Pozzilli; Didac Mauricio; Marc Y Donath; Luis Castaño; Ana Wägner; Hans Henrik Lervang; Hans Perrild; Thomas Mandrup-Poulsen Journal: Lancet Date: 2013-04-05 Impact factor: 79.321
Authors: Sharad Purohit; Ashok Sharma; Diane Hopkins; Leigh Steed; Bruce Bode; Stephen W Anderson; John Chip Reed; R Dennis Steed; Tao Yang; Jin-Xiong She Journal: J Clin Endocrinol Metab Date: 2015-07-09 Impact factor: 5.958
Authors: Mark A Atkinson; Jeffrey A Bluestone; George S Eisenbarth; Matthias Hebrok; Kevan C Herold; Domenico Accili; Massimo Pietropaolo; Peter R Arvan; Matthias Von Herrath; Dorene S Markel; Christopher J Rhodes Journal: Diabetes Date: 2011-05 Impact factor: 9.461
Authors: H Levy; X Wang; M Kaldunski; S Jia; J Kramer; S J Pavletich; M Reske; T Gessel; M Yassai; M W Quasney; M K Dahmer; J Gorski; M J Hessner Journal: Genes Immun Date: 2012-09-13 Impact factor: 2.676