{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:25:36Z","timestamp":1773847536095,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1993,2,1]],"date-time":"1993-02-01T00:00:00Z","timestamp":728524800000},"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":[[1993,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor necrosis factor-\u03b1 (TNF), an inflammatory cytokine released by macrophages, may be a mediator of lung injury during septicemia. We previously reported that the cyclooxygenase inhibitor ibuprofen and histamine receptor antagonists Cimetidine (H2 antagonist) and diphenhydramine (Hj antagonist) attenuate lung injury and reduce circulating TNF surges during porcine sepsis. Since pulmonary alveolar macrophages (PAM) may participate in early sepsis by producing TNF, we hypothesized that the TNF activity of PAM is reduced by ibuprofen, Cimetidine, and diphenhydramine. To test this, we examined changes in PAM-derived TNF bioactivity and cell viability of freshly isolated porcine PAM during exposure to bacterial endotoxin (LPS), ibuprofen, Cimetidine, and diphenhydramine. The TNF activity (% L929 cytotoxicity of PAM conditioned medium) was elevated in LPS-stimulated PAM cultures (15 to 25% increase at 1 to 6 h and 40 to 43% increase at 6 to 48 h, compared with non-LPS-stimulated cultures), and ibuprofen (150 \u00b5g\/ml) added with LPS decreased the TNF activity for 24 h (20 to 28% reduction at 1 to 24 h). Ibuprofen added 1 h after LPS was less effective in reducing the PAM-derived TNF activity (20 to 22% reduction at 2 to 6 h). Cimetidine (112 \u00b5g\/ml) reduced the TNF activity of LPS-stimulated PAM cultures during the first 4 h of LPS exposure (15 to 24% decrease at 1 to 4 h). Diphenhydramine (150 \u00b5g\/ml) attenuated the PAM-derived TNF activity but also decreased viability of PAM, indicating a toxic effect of this agent on PAM. These findings suggest that ibuprofen and Cimetidine attenuate the TNF bioactivity of PAM and that the cytotoxicity of agents that reduce TNF activity must be noted concurrently with studies examining attenuation of cellular TNF activity.<\/jats:p>","DOI":"10.1165\/ajrcmb\/8.2.169","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T22:36:00Z","timestamp":1365028560000},"page":"169-175","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacologic Reduction in Tumor Necrosis Factor Activity of Pulmonary Alveolar Macrophages"],"prefix":"10.1093","volume":"8","author":[{"given":"Sandra K.","family":"Leeper-Woodford","sequence":"first","affiliation":[{"name":"Departments of Medicine, Surgery, and Pathology, Virginia Commonwealth University\/Medical College of Virginia, Richmond, Virginia and Department of Basic Sciences\/Physiology, Mercer University School of Medicine, Macon, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard J.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Surgery, and Pathology, Virginia Commonwealth University\/Medical College of Virginia, Richmond, Virginia and Department of Basic Sciences\/Physiology, Mercer University School of Medicine, Macon, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey J.","family":"Sugerman","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Surgery, and Pathology, Virginia Commonwealth University\/Medical College of Virginia, Richmond, Virginia and Department of Basic Sciences\/Physiology, Mercer University School of Medicine, Macon, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"\u03b1 A.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Surgery, and Pathology, Virginia Commonwealth University\/Medical College of Virginia, Richmond, Virginia and Department of Basic Sciences\/Physiology, Mercer University School of Medicine, Macon, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1993,2,1]]},"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/8\/2\/169\/67276336\/ajrcmb_8_2_169.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/8\/2\/169\/67276336\/ajrcmb_8_2_169.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:57:01Z","timestamp":1773827821000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/8\/2\/169\/8511443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,2,1]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1993,2,1]]},"published-print":{"date-parts":[[1993,2,1]]}},"URL":"https:\/\/doi.org\/10.1165\/ajrcmb\/8.2.169","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1993,2]]},"published":{"date-parts":[[1993,2,1]]}}}