{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:15:06Z","timestamp":1773098106976,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pattern recognition receptors (PRR) are responsible for detecting pathogens and danger signals in organisms. Toll\u2010like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and some danger\u2010associated molecular patterns (DAMPs). Activation of this receptor initiates sickness behavior. Fever is a hallmark of this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We hypothesized that TLR4 signal inhibitors may have antipyretic activity. We evaluated the effect of TLR4 signal inhibitors on LPS or carrageenan\u2010induced fever in male Wistar rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Core body temperature was measured via telemetric implants. Fever was induced by injection of LPS (\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>E. coli<\/jats:italic>\n                      <\/jats:styled-content>\n                      O111:B4, 250\u2009\u03bcg\/kg, sc) or carrageenan (50\u2009mg\/kg, sc). For TLR4 signal inhibition, LPS from\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Rhodobacter sphaeroides<\/jats:italic>\n                      <\/jats:styled-content>\n                      (LPS\u2010RS), IAXO\u2010102, or naltrexone was used. Intracardiac blood samples were collected for measurement of interleukin\u20106 (IL\u20106), an endogenous pyrogen cytokine in plasma, by ELISA during the initial phase of LPS\u2010induced fever.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LPS\u2010RS pretreatment (25 or 100\u2009\u03bcg\/kg, sc) did not inhibit LPS\u2010induced fever and plasma IL\u20106 elevation. Other alternative TLR4 signal inhibitors, such as IAXO\u2010102 (3\u2009mg\/kg, sc) or naltrexone (10\u2009mg\/kg, sc), also failed to abolish LPS\u2010induced fever. An intriguing finding is that LPS\u2010RS or naltrexone inhibited the fever caused by carrageenan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Data show that TLR4 signal inhibitors have differential antipyretic activity on fever suggesting that some alternative or complementary mechanisms might be operational for LPS\u2010induced fever. Data also suggest that TLR4 signal inhibitors may be an alternative as a possible treatment option for DAMP\u2010mediated clinical pathologies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/fcp.70059","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T16:18:49Z","timestamp":1765383529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Antipyretic Effects of Toll\u2010Like Receptor 4 Signal Inhibitors in Male Rats"],"prefix":"10.1111","volume":"40","author":[{"given":"Tu\u011f\u00e7e","family":"Nomeno\u011flu","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0130brahim\u00a0Mert","family":"Y\u00fcksel","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soner","family":"Mamuk","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7336-185X","authenticated-orcid":false,"given":"Ey\u00fcp\u00a0Sabri","family":"Akarsu","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Ankara University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3843"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010016\u20101375\u20105"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00786.2006"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1994.266.1.R125"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102005\u201011\u20104743"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/AJPREGU.00408.2005"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.050"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010032414\u2010112240"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1189\/JLB.1104648"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CARBPOL.2009.01.020"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLIMM.2019.02.020"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M708833200"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JEP.2010.02.029"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2016.10.005"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3159"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2011.05.014"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHYSBEH.2020.113127"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp\u20102015\u20100219"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMBIO.2015.06.016"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/JM801333M\/SUPPL_FILE\/JM801333M_SI_001.PDF"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ATHEROSCLEROSIS.2015.08.010"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2008.06321.x"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11373\u2010005\u20100647\u2010x"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2003.12.001"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/ARCHOPHT.126.4.501"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/367990"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.04.017"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(94)91908\u20109"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23151"},{"key":"e_1_2_13_31_1","unstructured":"InvivoGen \u201cLPS\u2010RS Lipopolysaccharide fromRhodobacter sphaeroides\u2010TLR4 antagonist Catalog # 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