{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:35:21Z","timestamp":1791045321218,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Splice variants of the interleukin-4 (IL-4) cytokine gene have been described for humans, mice, and cattle. IL-4 splice variants have been shown to inhibit IL-4-mediated cellular responses and thus act as IL-4 antagonists. Recent work has highlighted the possibility of a correlation between IL-4 splice variants and protection against clinical tuberculosis. In this study we investigated the potential role of IL-4 splice variants IL-4\u03b42 and IL-4\u03b43 in cattle with bovine tuberculosis, using quantitative real-time reverse transcription-PCR. For this analysis we used naturally exposed tuberculin skin test-positive field reactor cattle, uninfected control cattle, and cattle from two experimental models of protective immunity against<jats:italic>Mycobacterium bovis<\/jats:italic>: (i) vaccination with<jats:italic>M. bovis<\/jats:italic>BCG and challenge with virulent<jats:italic>M. bovis<\/jats:italic>and (ii) infection with<jats:italic>M. bovis<\/jats:italic>and treatment with isoniazid (INH) prior to rechallenge. The cytokine levels of field reactor cattle were compared to the levels of uninfected controls, while in kinetic studies of BCG vaccination and INH treatment we compared pre-experimental values with sequential samples for each individual animal. The data revealed a significant increase in IL-4\u03b43 mRNA expression in field reactor cattle, which had no visible pathology compared to cattle with gross pathology typical of bovine tuberculosis. Increased IL-4\u03b43 expression in both cattle models of protective immunity (BCG vaccination and INH treatment) was transient over time, reaching significance in the INH treatment model. Our results support the hypothesis that IL-4\u03b43 is involved in protective immunity against<jats:italic>M. bovis<\/jats:italic>infection in cattle and are in accordance with clinical studies that have suggested a role for IL-4 splice variants in protective immunity in tuberculosis.<\/jats:p>","DOI":"10.1128\/iai.01932-06","type":"journal-article","created":{"date-parts":[[2007,3,27]],"date-time":"2007-03-27T01:13:09Z","timestamp":1174957989000},"page":"3006-3013","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Is Interleukin-4\u03b43 Splice Variant Expression in Bovine Tuberculosis a Marker of Protective Immunity?"],"prefix":"10.1128","volume":"75","author":[{"given":"Shelley G.","family":"Rhodes","sequence":"first","affiliation":[{"name":"Veterinary Laboratories Agency, Surrey KT15 3NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Sawyer","sequence":"additional","affiliation":[{"name":"Veterinary Laboratories Agency, Surrey KT15 3NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam O.","family":"Whelan","sequence":"additional","affiliation":[{"name":"Veterinary Laboratories Agency, Surrey KT15 3NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian S.","family":"Dean","sequence":"additional","affiliation":[{"name":"Veterinary Laboratories Agency, Surrey KT15 3NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Coad","sequence":"additional","affiliation":[{"name":"Veterinary Laboratories Agency, Surrey KT15 3NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie J.","family":"Ewer","sequence":"additional","affiliation":[{"name":"Veterinary Laboratories Agency, Surrey KT15 3NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas S.","family":"Waldvogel","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, University of Berne, Berne CH-3001, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Zakher","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, University of Berne, Berne CH-3001, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Clifford","sequence":"additional","affiliation":[{"name":"Veterinary Laboratories Agency, Surrey KT15 3NB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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