{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:31:52Z","timestamp":1782948712511,"version":"3.54.5"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"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":[[2010,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The mechanism of action of diethylcarbamazine (DEC), an antifilarial drug effective against tropical pulmonary eosinophilia, remains controversial. DEC effects on microfilariae depend on inducible NO synthase (iNOS). In eosinophilic pulmonary inflammation, its therapeutic mechanism has not been established. We previously described the rapid up-regulation of bone marrow eosinophilopoiesis in ovalbumin (OVA)-sensitized mice by airway allergen challenge, and further evidenced the down-regulation of eosinophilopoiesis by iNOS- and CD95L-dependent mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated whether: (1) DEC can prevent the effects of airway challenge of sensitized mice on lungs and bone marrow, and (2) its effectiveness depends on iNOS\/CD95L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>OVA-sensitized BALB\/c mice were intranasally challenged for 3 consecutive days, with DEC administered over a 12-, 3-, or 2-day period, ending at the day of the last challenge. We evaluated: (1) airway resistance, cytokine (IFN-\u03b3, IL-4, IL-5, and eotaxin) production, and pulmonary eosinophil accumulation; and (2) bone marrow eosinophil numbers in vivo and eosinophil differentiation ex vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>DEC effectively prevented the effects of subsequent challenges on: (1) airway resistance, Th1\/Th2 cytokine production, and pulmonary eosinophil accumulation; and (2) eosinophilopoiesis in vivo and ex vivo. Recovery from unprotected challenges included full responses to DEC during renewed challenges. DEC directly suppressed IL-5\u2013dependent eosinophilopoiesis in naive bone marrow. DEC was ineffective in CD95L-deficient gld mice and in mice lacking iNOS activity because of gene targeting or pharmacological blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DEC has a strong impact on pulmonary eosinophilic inflammation in allergic mice, as well as on the underlying hemopoietic response, suppressing the eosinophil lineage by an iNOS\/CD95L-dependent mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200905-0800oc","type":"journal-article","created":{"date-parts":[[2009,12,10]],"date-time":"2009-12-10T22:30:01Z","timestamp":1260484201000},"page":"429-437","source":"Crossref","is-referenced-by-count":36,"title":["Inducible Nitric Oxide Synthase\/CD95L-dependent Suppression of Pulmonary and Bone Marrow Eosinophilia by Diethylcarbamazine"],"prefix":"10.1093","volume":"181","author":[{"given":"Tulio","family":"Queto","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Humana, IFF, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Xavier-Elsas","sequence":"additional","affiliation":[{"name":"Department of Immunology, IMPPG, UFRJ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Aranha","family":"Gardel","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Humana, IFF, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"de Luca","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Humana, IFF, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica","family":"Barradas","sequence":"additional","affiliation":[{"name":"Department of Immunology, IMPPG, UFRJ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Masid","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Humana, IFF, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Machado R.","family":"e Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o, IOC, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestrutura, Instituto Aggeu Magalh\u00e3es, FIOCRUZ and Laborat\u00f3rio de Microscopia e Microan\u00e1lise, Centro de Tecnologias Estrat\u00e9gicas do Nordeste, Recife, Brazil; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilton Meira F.","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Humana, IFF, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane P.","family":"Dias","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Patologia, Faculdade de Medicina, Universidade Federal, Fluminense, Niteroi, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Ignez","family":"Gaspar-Elsas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Humana, IFF, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,3,1]]},"reference":[{"key":"2026032102151545000_BIB1","first-page":"S49","volume-title":"Parasitology","year":"1992"},{"key":"2026032102151545000_BIB2","first-page":"E95","volume-title":"Front Biosci","year":"2000"},{"key":"2026032102151545000_BIB3","first-page":"3351","volume-title":"Infect Immun","year":"1996"},{"key":"2026032102151545000_BIB4","first-page":"4","volume-title":"Filaria J","year":"2005"},{"key":"2026032102151545000_BIB5","first-page":"201","volume-title":"Parasitol Res","year":"2005"},{"key":"2026032102151545000_BIB6","first-page":"217","volume-title":"Exp Parasitol","year":"1998"},{"key":"2026032102151545000_BIB7","first-page":"1123","volume-title":"Clin Infect Dis","year":"2004"},{"key":"2026032102151545000_BIB8","first-page":"418","volume-title":"Ann Allergy","year":"1971"},{"key":"2026032102151545000_BIB9","first-page":"2129","volume-title":"Biochem Pharmacol","year":"1982"},{"key":"2026032102151545000_BIB10","first-page":"661","volume-title":"J Appl Physiol","year":"2004"},{"key":"2026032102151545000_BIB11","first-page":"184","volume-title":"Nitric Oxide","year":"2004"},{"key":"2026032102151545000_BIB12","first-page":"1187","volume-title":"Clin Exp Allergy","year":"2009"},{"key":"2026032102151545000_BIB13","first-page":"528","volume-title":"Br J Pharmacol","year":"2008"},{"key":"2026032102151545000_BIB14","first-page":"727","volume-title":"Curr Opin Immunol","year":"2001"},{"key":"2026032102151545000_BIB15","first-page":"404","volume-title":"Am J Respir Cell Mol Biol","year":"1997"},{"key":"2026032102151545000_BIB16","first-page":"3864","volume-title":"Infect Immun","year":"1999"},{"key":"2026032102151545000_BIB17","first-page":"66","volume-title":"Am J Respir Cell Mol Biol","year":"2009"},{"key":"2026032102151545000_BIB18","first-page":"766","volume-title":"Am J Respir Crit Care Med","year":"1997"},{"key":"2026032102151545000_BIB19","first-page":"345S","volume-title":"Chest","year":"2003"},{"key":"2026032102151545000_BIB20","first-page":"333","volume-title":"Blood","year":"2001"},{"key":"2026032102151545000_BIB21","first-page":"285","volume-title":"J Leukoc Biol","year":"1996"},{"key":"2026032102151545000_BIB22","first-page":"192","volume-title":"Trans R Soc Trop Med Hyg","year":"1996"},{"key":"2026032102151545000_BIB23","first-page":"1773","volume-title":"Science","year":"2004"},{"key":"2026032102151545000_BIB24","first-page":"1776","volume-title":"Science","year":"2004"},{"key":"2026032102151545000_BIB25","first-page":"97","volume-title":"Cytokine Growth Factor Rev","year":"2009"},{"key":"2026032102151545000_BIB26","first-page":"11","volume-title":"Vet J","year":"1997"},{"key":"2026032102151545000_BIB27","first-page":"272","volume-title":"Parasitol Res","year":"2002"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/181\/5\/429\/67309321\/ajrccm_181_5_429.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/181\/5\/429\/67309321\/ajrccm_181_5_429.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T06:15:23Z","timestamp":1774073723000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/181\/5\/429\/8515463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,1]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2010,3,1]]},"published-print":{"date-parts":[[2010,3,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200905-0800oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,3]]},"published":{"date-parts":[[2010,3,1]]}}}