{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:02:06Z","timestamp":1788184926282,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3561,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Tumour necrosis factor (TNF\u2010\u03b1) is a pleiotropic cytokine which is deeply involved in the pathogenesis of splanchnic artery occlusion (SAO) shock. Tacrolimus, formerly known as FK506, is a macrolide antibiotic, that blocks the transcription of several proinflammatory cytokines including TNF\u2010\u03b1.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45\u2003min. This surgical procedure resulted in an irreversible state of shock (SAO shock). Sham operated animals were used as controls. SAO shocked rats had a decreased survival rate (0% at 4\u2003h of reperfusion, while sham shocked rats survived more than 4\u2003h), enhanced serum TNF\u2010\u03b1 concentrations (415\u00b112\u2003U\u2003ml<jats:sup>\u22121<\/jats:sup>), decreased mean arterial blood pressure (MAP), leukopenia and increased ileal leukocyte accumulation studied by means of myeloperoxidase activity (MPO=7.5\u00b10.3\u2003U\u2003g<jats:sup>\u22121<\/jats:sup> tissue). Moreover aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1\u2003n<jats:sc>M<\/jats:sc>\u201310\u2003\u03bc<jats:sc>M<\/jats:sc>), reduced responsiveness to acetylcholine (ACh, 10\u2003n<jats:sc>M<\/jats:sc>\u201310\u2003\u03bc<jats:sc>M<\/jats:sc>) and increased staining for intercellular adhesion molecule\u20101 (ICAM\u20101). Furthermore increased mRNA for TNF\u2010\u03b1 was observed in peritoneal macrophages of SAO shocked rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tacrolimus (100\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>, 5\u2003min after splanchnic arteries occlusion) increased survival rate (SAO+Tacrolimus=100% at 4\u2003h of reperfusion), reverted the marked hypotension, reduced serum TNF\u2010\u03b1 (15\u00b13\u2003U\u2003ml<jats:sup>\u22121<\/jats:sup>), ameliorated leukopenia, reduced ileal MPO (0.9\u00b10.01\u2003U\u2003g<jats:sup>\u22121<\/jats:sup> tissue), restored to control values the hyporeactivity to PE, improved the reduced responsiveness to ACh and blunted the enhanced immunostaining for ICAM\u20101 in the aorta. Finally tacrolimus suppressed cytokine mRNA levels in peritoneal macrophages.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The data suggest that tacrolimus may represent a new therapeutic approach in circulatory shock.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>127<\/jats:bold>, 498\u2013504; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702528\">10.1038\/sj.bjp.0702528<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702528","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:03:49Z","timestamp":1106942629000},"page":"498-504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tacrolimus suppresses tumour necrosis factor\u2010\u03b1 and protects against splanchnic artery occlusion shock"],"prefix":"10.1111","volume":"127","author":[{"given":"Francesco","family":"Squadrito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Altavilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Squadrito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Ferlito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe M","family":"Campo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarita","family":"Arlotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafino","family":"Grimaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Quartarone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Saitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille P","family":"Caputi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1994.tb02503.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(89)90055-6"},{"key":"e_1_2_6_4_1","first-page":"G275","article-title":"Beneficial effects of two forms of NO administration in feline splanchnic artery occlusion shock","volume":"321","author":"AOKI N.","year":"1990","journal-title":"Am. J. Physiol."},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.12.3724"},{"key":"e_1_2_6_6_1","first-page":"2850","article-title":"FK506 and rapamycin: molecular probes of T\u2010lymphocyte activation","volume":"23","author":"BIERERBE","year":"1991","journal-title":"Transplant. Proc."},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(90)81445-T"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199409150-00011"},{"key":"e_1_2_6_9_1","first-page":"15","volume-title":"Immunosuppressive drugs: developments in anti\u2010rejection therapy","author":"FRUMAN D.A.","year":"1994"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(88)90080-5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1995.1180"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.70.43"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/75.5.734"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)00452-8"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.1256"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-199803000-00009"},{"key":"e_1_2_6_17_1","first-page":"109","article-title":"Nitric oxide: physiology, pathophysiology and pharmacology","volume":"43","author":"MONCADA S.","year":"1991","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0160-5402(85)90029-4"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53220-8"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(94)00683-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.11.5736"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.4049\/jimmunol.125.4.1671","article-title":"Purification and physicochemical characterization of rabbit tumor necrosis factor","volume":"125","author":"RUFF M.R.","year":"1980","journal-title":"J. Immunol."},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(93)90206-I"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1702904"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/331624a0"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb17118.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb17079.x"},{"key":"e_1_2_6_28_1","first-page":"236","article-title":"Passive immunization with antibodies against tumor necrosis factor TNF\u2010\u03b1 protects from the lethality of splanchnic artery occlusion shock","volume":"37","author":"SQUADRITO F.","year":"1992","journal-title":"Circ. Shock."},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15672.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199408000-00011"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1376003"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(92)90262-N"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.1.267"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00126-7"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1076\/ocii.6.1.51.8079"},{"key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1749-6632.1993.tb17137.x","article-title":"The mechanisms of action of FK506 and cyclosporin\u2003A","volume":"699","author":"WIEDERRECHT G.","year":"1993","journal-title":"Ann. N.Y. Acad. Sci."}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702528","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702528","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0702528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T22:59:53Z","timestamp":1698533993000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0702528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1999,5]]}},"alternative-id":["10.1038\/sj.bjp.0702528"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0702528","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,5]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}