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In the presence of 10<jats:sup>\u22126<\/jats:sup> M dexamethasone \u03b2\u2010fibrinogen mRNA levels increased 6\u2010fold after addition of recombinant human IL6 (rhIL6). rhIL1\u03b2 or recombinant human tumor necrosis factor a (rhTNF\u03b1) had essentially no effect on \u03b2\u2010fibrinogen mRNA induction but led to a 20\u2010fold increase in \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein mRNA in the presence of dexamethasone. On the other hand, rhIL6 was a much weaker stimulator of \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein mRNA synthesis. All three mediators reduced albumin mRNA concentrations to about 30% of controls.<\/jats:p><jats:p>Whereas the induction of \u03b2\u2010fibrinogen mRNA was potentiated by dexamethasone, the synthetic glucocorticoid analog was an absolute requirement for the stimulation of \u03b1<jats:sub>l<\/jats:sub>\u2010acid glycoprotein mRNA. The mRNA levels of the negative acute\u2010phase protein albumin were induced 5\u2010fold by dexamethasone alone. The \u03b2\u2010fibrinogen mRNA induction started immediately after addition of rhIL6 and reached a maximum between 12 and 18 h. In contrast, the time\u2010course for \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein mRNA synthesis showed a lag phase of 8 h followed by an increase up to 20 h after rhIL 1\u03b2. RhTNF\u03b1 led to an even more delayed increase in \u03b1<jats:sub>l<\/jats:sub>\u2010acid glycoprotein mRNA. Whereas in the case of \u03b2\u2010fibrinogen mRNA induction no synergistic effect was observed between various concentrations of the three mediators, the combination of rhIL6\/rhIL1\u03b2 as well as rhIL6\/rhTNF\u03b1 or rhIL 1\u03b2\/rhTNF\u03b1 regulated synergistically \u03b1<jats:sub>1<\/jats:sub>\u2010acid glycoprotein and albumin mRNA. It is concluded that discrete acute\u2010phase proteins are regulated differently by the inflammatory mediators IL6, IL1\u03b2 and TNF\u03b1, indicating that the acute\u2010phase response is more complex than previously assumed.<\/jats:p><jats:p>The Fao cell line used in this study turned out to be an ideal model for acute\u2010phase protein regulation, suitable for the discrimination between the inflammatory mediators IL6 and IL1\/TNF\u03b1.<\/jats:p>","DOI":"10.1002\/eji.1830180513","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T05:37:56Z","timestamp":1172727476000},"page":"739-746","source":"Crossref","is-referenced-by-count":198,"title":["Action of recombinant human interleukin 6, interleukin 1\u03b2 and tumor necrosis factor \u03b1 on the mRNA induction of acute\u2010phase proteins"],"prefix":"10.1002","volume":"18","author":[{"given":"Tilo","family":"Andus","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Geiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadamitsu","family":"Kishimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.","family":"Heinrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,22]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1982.tb22124.x"},{"key":"e_1_2_1_3_2","first-page":"139","volume-title":"The acute\u2010phase response to injury and infection","author":"Koj A.","year":"1985"},{"key":"e_1_2_1_4_2","first-page":"423","volume-title":"Plasma Protein Secretion by the Liver","author":"Schreiber G.","year":"1983"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(81)90513-1"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)69917-5"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.8.4718"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(81)80191-X"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)68627-8"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(83)81033-3"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1983.tb07823.x"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365517209102760"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(77)90415-6"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109551"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/285498a0"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1982.tb22146.x"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)39876-9"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2240505"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(85)81298-9"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198411293112205"},{"key":"e_1_2_1_21_2","first-page":"23","volume-title":"The Acute Phase Response to Injury and Infection","author":"Sipe J. 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