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In this study, we used the newly synthesized compound S18407, which is a prodrug of the active drug S16197, to analyze the functional importance of \u03b14\u03b21-dependent cell adhesion for the development of arthritis and for the antibacterial immune response. S16197 is shown to interfere specifically with the binding of \u03b14\u03b21 integrin to its ligands VCAM-1 and fibronectin in vitro. Treatment of B. burgdorferi-infected C3H\/HeJ mice with the \u03b14\u03b21 antagonist significantly ameliorated the outcome of clinical arthritis and the influx of neutrophilic granulocytes into ankle joints. Furthermore, local mRNA up-regulation of the proinflammatory mediators IL-1, IL-6, and cyclooxygenase-2 was largely abolished. Neither the synthesis of spirochete-specific Igs nor the development of a Th1-dominated immune response was altered by the treatment. Importantly, the drug also did not interfere with Ab-mediated control of spirochete load in the tissues. These findings demonstrate that the pathogenesis, but not the protective immune response, in Lyme arthritis is dependent on the \u03b14\u03b21-mediated influx of inflammatory cells. The onset of inflammation can be successfully targeted by treatment with S18407.<\/jats:p>","DOI":"10.4049\/jimmunol.175.7.4724","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:55:01Z","timestamp":1398034501000},"page":"4724-4734","source":"Crossref","is-referenced-by-count":17,"title":["A Small Molecule \u03b14\u03b21 Antagonist Prevents Development of Murine Lyme Arthritis without Affecting Protective Immunity"],"prefix":"10.1093","volume":"175","author":[{"given":"Joachim","family":"Gla\u0308sner","sequence":"first","affiliation":[{"name":"Institute for Clinical Microbiology, Immunology, and Hygiene, University of Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Blum","sequence":"additional","affiliation":[{"name":"Aventis Pharma Deutschland GmbH, a company of the Sanofi-Aventis Group, Frankfurt am Main ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volkmar","family":"Wehner","sequence":"additional","affiliation":[{"name":"Aventis Pharma Deutschland GmbH, a company of the Sanofi-Aventis Group, Frankfurt am Main ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Ulrich","family":"Stilz","sequence":"additional","affiliation":[{"name":"Aventis Pharma Deutschland GmbH, a company of the Sanofi-Aventis Group, Frankfurt am Main ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan D","family":"Humphries","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G Paul","family":"Curley","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Paul","family":"Mould","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J","family":"Humphries","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupert","family":"Hallmann","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, University Hospital , Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Ro\u0308llinghoff","sequence":"additional","affiliation":[{"name":"Institute for Clinical Microbiology, Immunology, and Hygiene, University of Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre\u0301","family":"Gessner","sequence":"additional","affiliation":[{"name":"Institute for Clinical Microbiology, Immunology, and Hygiene, University of Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,10,1]]},"reference":[{"key":"2026020212185109100_R1","first-page":"63","volume-title":"Annu. 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