Circadian rhythms and rheumatoid arthritis

Maurizio Cutolo

Research output: Contribution to journalShort survey

1 Citation (Scopus)

Abstract

Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of pro-inflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the night (night release). The impressive positive results observed in RA patients treated with modified-night release prednisone with a low-dose chronotherapy, seem applicable even for other agents such as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained by the night time daily administration of methotrexate. Interestingly, a very recent study showed that methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is promising.

Original languageEnglish
Pages (from-to)327-333
Number of pages7
JournalJoint Bone Spine
Volume86
Issue number3
DOIs
Publication statusPublished - May 2019
Externally publishedYes

Keywords

  • Chronotherapy
  • Circadian rhythms
  • Connective tissue diseases
  • Glucocorticoids
  • Methotrexate
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology

Cite this

Circadian rhythms and rheumatoid arthritis. / Cutolo, Maurizio.

In: Joint Bone Spine, Vol. 86, No. 3, 05.2019, p. 327-333.

Research output: Contribution to journalShort survey

Cutolo, Maurizio. / Circadian rhythms and rheumatoid arthritis. In: Joint Bone Spine. 2019 ; Vol. 86, No. 3. pp. 327-333.
@article{85c3e708270341cd9930b5a3b98ada87,
title = "Circadian rhythms and rheumatoid arthritis",
abstract = "Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of pro-inflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the night (night release). The impressive positive results observed in RA patients treated with modified-night release prednisone with a low-dose chronotherapy, seem applicable even for other agents such as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained by the night time daily administration of methotrexate. Interestingly, a very recent study showed that methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is promising.",
keywords = "Chronotherapy, Circadian rhythms, Connective tissue diseases, Glucocorticoids, Methotrexate, Rheumatoid arthritis",
author = "Maurizio Cutolo",
year = "2019",
month = "5",
doi = "10.1016/j.jbspin.2018.09.003",
language = "English",
volume = "86",
pages = "327--333",
journal = "Revue du Rhumatisme (English Edition)",
issn = "1169-8446",
publisher = "Elsevier Masson",
number = "3",

}

TY - JOUR

T1 - Circadian rhythms and rheumatoid arthritis

AU - Cutolo, Maurizio

PY - 2019/5

Y1 - 2019/5

N2 - Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of pro-inflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the night (night release). The impressive positive results observed in RA patients treated with modified-night release prednisone with a low-dose chronotherapy, seem applicable even for other agents such as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained by the night time daily administration of methotrexate. Interestingly, a very recent study showed that methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is promising.

AB - Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of pro-inflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the night (night release). The impressive positive results observed in RA patients treated with modified-night release prednisone with a low-dose chronotherapy, seem applicable even for other agents such as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained by the night time daily administration of methotrexate. Interestingly, a very recent study showed that methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is promising.

KW - Chronotherapy

KW - Circadian rhythms

KW - Connective tissue diseases

KW - Glucocorticoids

KW - Methotrexate

KW - Rheumatoid arthritis

UR - http://www.scopus.com/inward/record.url?scp=85054441641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054441641&partnerID=8YFLogxK

U2 - 10.1016/j.jbspin.2018.09.003

DO - 10.1016/j.jbspin.2018.09.003

M3 - Short survey

C2 - 30227223

AN - SCOPUS:85054441641

VL - 86

SP - 327

EP - 333

JO - Revue du Rhumatisme (English Edition)

JF - Revue du Rhumatisme (English Edition)

SN - 1169-8446

IS - 3

ER -