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In the present study, we extended these observations by showing that moderate hypothermia exerts effects on TNF-\u03b1 and IL-1\u03b2 generation in the human THP-1 monocyte cell line that are similar to those that we previously found in primary cultured monocytes; that hypothermia causes comparable changes in cytokine generation stimulated by zymosan, toxic shock syndrome toxin-1, and LPS; and that hypothermia causes similar changes in TNF-\u03b1 and IL-1\u03b2 mRNA accumulation. TNF-\u03b1 mRNA half-life, determined after transcriptional arrest with actinomycin D, was not significantly prolonged by lowering incubation temperature from 37 to 32\u00b0C, suggesting that hypothermia modifies TNF-\u03b1 gene transcription. This finding was further supported by reporter gene studies showing a threefold increase in activity of the human TNF-\u03b1 promoter at 32 vs. 37\u00b0C. Electrophoretic mobility shift assay revealed that hypothermia prolonged NF-\u03ba\u0392 activation, identifying a potential role for this transcription factor in mediating the effects of hypothermia on TNF-\u03b1 and IL-1\u03b2 production. Delayed reexpression of the inhibitor I\u03baB\u03b1, shown by Northern blotting and immunoblotting, may account in part for the prolonged NF-\u03ba\u0392 activation at 32\u00b0C. Augmentation of NF-\u03ba\u0392-dependent gene expression during prolonged exposure to hypothermia may be a common mechanism leading to increased lethality in sepsis, late-onset systemic inflammatory response syndrome after accidental hypothermia, and neuroprotection after ischemia. <\/jats:p>","DOI":"10.1152\/ajpcell.00507.2003","type":"journal-article","created":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T00:23:19Z","timestamp":1081815799000},"page":"C422-C431","source":"Crossref","is-referenced-by-count":79,"title":["Hypothermia prolongs activation of NF-\u03ba\u0392 and augments generation of inflammatory cytokines"],"prefix":"10.1152","volume":"287","author":[{"given":"Karen D.","family":"Fairchild","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishwar S.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth E.","family":"Drysdale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose M.","family":"Viscardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Hester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Lazusky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Hasday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Arenzana-Seisdedos F, Thompson J, Rodriguez MS, Bachelerie F, Thomas D, and Hay RT. 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