{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:45:56Z","timestamp":1787021156129,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T00:00:00Z","timestamp":1151625600000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:sc>Abstract:\u2002<\/jats:sc>\n                    <\/jats:bold>\n                    <jats:bold>Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time\u2010dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time\u2010dependent inflammatory reaction with effects opposite those of cortisol. Interestingly, cortisol and MLT show an opposite response to the light. The light conditions in the early morning have a strong impact on the morning cortisol peak, whereas MLT is synthesized in a strictly nocturnal pattern. Recently, a diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and related to immunomodulatory actions of cortisol and MLT. The interferon (IFN)\u2010\u03b3\/interleukin (IL)\u201010 ratio peaked during the early morning and correlated negatively with plasma cortisol and positively with plasma MLT. Accordingly, the intensity of the arthritic pain varies consistently as a function of the hour of the day: pain is greater after waking up in the morning than in the afternoon or evening. The reduced cortisol and adrenal androgen secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with glucocoticoids, should be clearly considered as a \u201crelative adrenal insufficiency\u201d in the presence of a sustained inflammatory process, and allows Th1 type cytokines to be produced in higher amounts during the late night. In conclusion, the right timing (early morning) for the glucocorticoid therapy in arthritis is fundamental and well justified by the circadian rhythms of the inflammatory mechanisms.<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1196\/annals.1351.027","type":"journal-article","created":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T15:35:49Z","timestamp":1153323349000},"page":"289-299","source":"Crossref","is-referenced-by-count":58,"title":["Circadian Rhythms"],"prefix":"10.1111","volume":"1069","author":[{"given":"MAURIZIO","family":"CUTOLO","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ALBERTO","family":"SULLI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CARMEN","family":"PIZZORNI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARIA ELENA","family":"SECCHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"STEFANO","family":"SOLDANO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BRUNO","family":"SERIOLO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RAINER H.","family":"STRAUB","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KATI","family":"OTSA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GEORGES J.","family":"MAESTRONI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,6,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.41.5.453"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(94)00082-E"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.284.6315.551"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1997.0289"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1210\/jcem.82.4.3852","article-title":"Circadian relationships between interleukin (IL)\u20106 and hypothalamic\u2010pituitary\u2010adrenal axis hormones: failure of IL\u20106 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis","volume":"82","author":"Crofford L.J.","year":"1997","journal-title":"J. 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