{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:52:12Z","timestamp":1790254332028,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"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":[[1999,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The maturation of eosinophils in bone marrow, their migration to pulmonary tissue, and their subsequent degranulation and release of toxic granule proteins contributes to the pathophysiology observed in asthma. Interleukin-5 (IL-5) is essential for these processes to occur. Therefore, much emphasis has been placed on attempts to inhibit the production or activity of IL-5 in order to attenuate the inflammatory aspect of asthma. In this report, the immunological consequences of long-term exposure to an antibody recognizing IL-5 (TRFK-5) were studied in a murine pulmonary inflammation model. A single dose of TRFK-5 (1 mg\/kg, intraperitoneally) reversibly inhibited antigen-dependent lung eosinophilia in mice for at least 12 wk and inhibited the release of eosinophils from bone marrow for at least 8 wk. Normal responses to aerosol challenge were attained after 24 wk. In mice treated acutely with antibody (2 h before challenge), 50% inhibition of pulmonary eosinophilia occurred when 0.06 mg\/kg TRFK-5 was administered (intraperitoneally; ED50), resulting in 230 ng\/ml (IC50) in serum. In mice treated with one dose of TRFK-5 (1 mg\/kg) and rested before challenge, the antibody exhibited a half-life of 2.4 wk. After 18 to 19 wk, antigen challenge-induced eosinophilia was inhibited by 50% and serum levels of TRFK-5 were 25 ng\/ml. TRFK-5 remaining in mice 8 wk after a single injection of TRFK-5 was sufficient to inhibit at least 50% of the eosinophilia induced in blood 3 h after injection of recombinant murine IL-5 (10 \u03bcg\/kg, intravenously). To assess the biologic effect of long-term exposure of mice to antibody, several parameters of immune-cell function were measured. Throughout the extended period of activity of TRFK-5 (\u2265 12 wk) there were no gross effects on antigen-dependent increases in T-cell recruitment into bronchoalveolar fluid (BALF), in IL-4 and IL-5 steady-state mRNA levels in lung tissue, or in immunoglobulin E (IgE) and IgG levels in serum. There was a small increase in IL-5 steady-state mRNA production in TRFK-5-treated mice after 2 h or 2 wk, but this was not observed at other times examined. In untreated mice, IL-5 steady-state mRNA production in response to antigen challenge decreased &amp;gt; 6-fold with age, although at all time points there was an increase in mRNA levels following challenge. Therefore, at later times, 25 ng\/ml rather than 230 ng\/ml of TRFK-5 inhibited BALF eosinophilia, probably because of reduced IL-5 levels. Twenty-four weeks after treatment with TRFK-5, when challenge-induced eosinophilia was restored, there was an excess of CD4+ T cells in BALF from challenged mice. However, these T cells had no measurable effects on other responses to challenge, including cytokine production, B-cell accumulation, and immunoglobulin production in serum. Thus, the biologic duration of TRFK-5 was several months, and its activity was due to the presence of antibody above a therapeutic threshold rather than to any profound effect on the immune system.<\/jats:p>","DOI":"10.1165\/ajrcmb.20.2.3327","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T21:55:44Z","timestamp":1365026144000},"page":"248-255","source":"Crossref","is-referenced-by-count":57,"title":["Effects of Chronic Anti-Interleukin-5 Monoclonal Antibody Treatment in a Murine Model of Pulmonary Inflammation"],"prefix":"10.1093","volume":"20","author":[{"given":"Charles G.","family":"Garlisi","sequence":"first","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted T.","family":"Kung","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Minnicozzi","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby P.","family":"Umland","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Stelts","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Crawley","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Falcone","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce G.","family":"Myers","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Jones","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Motasim Billah","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Kreutner","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Egan","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1999,2,1]]},"reference":[{"key":"2026030700120160300_B1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/0091-6749(82)90038-0","article-title":"Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber.","volume":"70","author":"Cartier","year":"1982","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026030700120160300_B2","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1056\/NEJM199212313272708","article-title":"Asthma.","volume":"327","author":"McFadden","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"2026030700120160300_B3","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0065-2776(08)60491-5","article-title":"The pathobiology of bronchial asthma.","volume":"51","author":"Arm","year":"1992","journal-title":"Adv. Immunol."},{"key":"2026030700120160300_B4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0065-2776(08)60351-X","article-title":"The eosinophilic leukocyte: structure and function.","volume":"39","author":"Gleich","year":"1986","journal-title":"Adv. Immunol."},{"key":"2026030700120160300_B5","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1164\/ajrccm\/147.3.548","article-title":"Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs.","volume":"147","author":"Van Oosterhout","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700120160300_B6","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1164\/ajrccm.152.2.7633694","article-title":"Effects of an antibody to interleukin-5 in a monkey model of asthma.","volume":"152","author":"Mauser","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026030700120160300_B7"},{"key":"2026030700120160300_B8","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1164\/ajrccm\/146.2.374","article-title":"CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea.","volume":"146","author":"Nakajima","year":"1992","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700120160300_B9","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1164\/ajrccm\/146.1.263","article-title":"Interleukin-5 modulates eosinophil accumulation in allergic guinea pig lung.","volume":"146","author":"Gulbenkian","year":"1992","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700120160300_B10","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0014-2999(92)90273-7","article-title":"Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach.","volume":"211","author":"Chand","year":"1992","journal-title":"Eur. J. Pharmacol."},{"key":"2026030700120160300_B11","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1164\/ajrccm\/148.6_Pt_1.1623","article-title":"Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma.","volume":"148","author":"Mauser","year":"1993","journal-title":"Am. Rev. Respir. 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Allergy Immunol."},{"key":"2026030700120160300_B14","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1136\/thx.48.8.845","article-title":"Cytokines in asthma.","volume":"48","author":"Robinson","year":"1993","journal-title":"Thorax"},{"key":"2026030700120160300_B15","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1182\/blood.V79.12.3101.bloodjournal79123101","article-title":"Interleukin-5, eosinophils, and disease.","volume":"79","author":"Sanderson","year":"1992","journal-title":"Blood"},{"key":"2026030700120160300_B16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1136\/thx.52.5.483","article-title":"Anti-interleukin 5 strategies as a potential treatment for asthma.","volume":"52","author":"Singh","year":"1997","journal-title":"Thorax"},{"key":"2026030700120160300_B17","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1165\/ajrcmb.13.3.7654390","article-title":"Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody.","volume":"13","author":"Kung","year":"1995","journal-title":"Am. 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