{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:38:42Z","timestamp":1773758322989,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1999,3,1]],"date-time":"1999-03-01T00:00:00Z","timestamp":920246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We compared the effects of cyclosporin A (CSA) and a macrotetrolide antibiotic, dinactin, on human T-cell proliferation and cytokine production induced by stimulation of the T-cell receptor alone (monoclonal antibody [mAb] directed against CD3) or in combination with costimulatory signals (mAbs directed against CD3 and CD28). These agents were also examined in a murine model of interleukin (IL)-5\u2013mediated pulmonary inflammation. Dinactin inhibited T-cell proliferation induced by IL-2, by mAb to CD3, and by mAbs to CD3 plus \u03b1-CD28 with identical dose-response curves (IC50 = 10\u201320 ng\/ml). Dinactin inhibited cytokine production with IC50 values of 10 ng\/ml for IL-4 and IL-5 and 30 or 60 ng\/ml for interferon-\u03b3 or IL-2, respectively. Unlike CSA, exogenous IL-2 did not alter the dinactin-mediated effects on T cells, and nuclear run-on and steady-state messenger RNA (mRNA) analysis showed that dinactin inhibited cytokine production through a post-transcriptional mechanism. CSA selectively blocked T-cell receptor\u2013induced T-cell proliferation and cytokine production (IC50 = 10 ng\/ml). Under costimulatory conditions, IL-5 synthesis was only minimally inhibited by high concentrations of CSA, and at CSA concentrations of less than 125 ng\/ml, IL-5 was significantly increased above control values. Dinactin and CSA reduced pulmonary eosinophilia when administered within 1 d of airway antigen challenge. Of the cytokine mRNAs examined in the lungs of CSA-pretreated, antigen-challenged mice, IL-5 mRNA levels were the least reduced, paralleling the resistance of IL-5 to CSA observed in vitro and suggesting a role for CD28 in the in vivo induction of IL-5.<\/jats:p>","DOI":"10.1165\/ajrcmb.20.3.3266","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T21:53:09Z","timestamp":1365025989000},"page":"481-492","source":"Crossref","is-referenced-by-count":21,"title":["Effects of Cyclosporin A and Dinactin on T-Cell Proliferation, Interleukin-5 Production, and Murine Pulmonary Inflammation"],"prefix":"10.1093","volume":"20","author":[{"given":"Shelby P.","family":"Umland","sequence":"first","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himanshu","family":"Shah","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Jakway","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Shortall","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shad","family":"Razac","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles G.","family":"Garlisi","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Falcone","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ted T.","family":"Kung","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn","family":"Stelts","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinod","family":"Hegde","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Patel","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Motasim Billah","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert W.","family":"Egan","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1999,3,1]]},"reference":[{"key":"2026030700135331600_B1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/0167-5699(92)90026-4","article-title":"T cells and eosinophils in the pathogenesis of asthma.","volume":"13","author":"Corrigan","year":"1992","journal-title":"Immunol. 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