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Disease activity in rheumatoid arthritis: Studies in interleukin-6, tumour necrosis factor alpha, monocyte activity, acute phase markers, glucocorticoids, and disability
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the present studies, aspects of some disease activity measures in rheumatoid arthritis (RA) have been investigated, including the effect of glucocorticoids on this activity. In RA, serum interleukin(IL)-6 levels were elevated and were shown to have a circadian rhythm, with peak levels in the morning, declining towards low or normal levels in the afternoon and evening. In contrast, serum levels of tumour necrosis factor(TNF) alpha were low and stable. In other connective tissue diseases, serum TNF alpha levels were elevated but without circadian variation, while IL-6 levels were low and stable. Nocturnal administration (at 2:00 a.m.) of low-dose prednisolone a few hours before the early morning peak of IL-6 was shown to be significantly more effective in reducing clinical symptoms of disease activity and serum IL-6 levels than the traditional morning administration (at 7:30 a.m.) of the same dose of prednisolone. Circulating monocytes are activated in RA, expressing receptors related to adhesion and phagocytosis. Treatment with glucocorticoids suppressed the expression of these receptors on monocytes, and this may be one mechanism of the beneficial effect of glucocorticoids in RA. Endogenous levels of cortisol seem to play a minor role in expression of monocyte receptors. The different acute phase markers used to assess disease activity in RA showed good corrrelations with each other and with serum IL-6 levels. There were especially strong corrrelations between C-reactive protein (CRP) and Serum amyloid protein A (SAA), and between fibrinogen and erythrocyte sedimentation rate (ESR). Fibrinogen and CRP showed stronger correlation than ESR with the Modified Health Assessment Questionnaire (MHAQ) score and with the neutrophil count. Four simple objective function tests were each compared with the HAQ score a with a radiological joint damage score (Larsen score). The objective function tests correlated with the MHAQ score, and each of these two methods of assessing physical disability correlated with pain, CRP and ESR. In addition, most of the objective function tests correlated significantly with radiological joint damage, while the MHAQ score did not.

Place, publisher, year, edition, pages
Uppsala: Institutionen för medicinska vetenskaper , 2003. , p. 91
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1248
Keyword [en]
Chemistry, acute phase markers, circadian rhythm, disability, disease activity, glucocorticoids, monocyte activation, rheumatoid arthritis
Keyword [sv]
Kemi
National Category
Chemical Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:uu:diva-3373ISBN: 91-554-5594-8 (print)OAI: oai:DiVA.org:uu-3373DiVA, id: diva2:162541
Public defence
2003-05-19, Rosénsalen, Barnkliniken, Uppsala, 13:15
Opponent
Supervisors
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
List of papers
1. Circadian rhytm of serum interleukin-6 in rheumatoid arthritis
Open this publication in new window or tab >>Circadian rhytm of serum interleukin-6 in rheumatoid arthritis
Show others...
1994 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 53, no 8, p. 521-4Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES--To test the hypothesis of a diurnal variation in circulating levels of interleukin-6 (IL-6) and/or tumour necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis and other inflammatory connective tissue diseases. METHODS--Serum levels of IL-6 and TNF-alpha were measured at three hour intervals from 7:30 to 22:30 in 48 patients with different rheumatic diseases as well as ten healthy controls. In four of the patients with rheumatoid arthritis, serum IL-6 levels were measured before and after one week of treatment with prednisolone 15-20 mg daily. RESULTS--IL-6 and TNF-alpha could not be detected in serum from healthy controls. However, serum IL-6 levels were substantially increased in patients with rheumatoid arthritis. Furthermore, patients with rheumatoid arthritis showed a statistically significant circadian variation in levels of IL-6. Peak values appeared in the morning and low values in the afternoon and evening. In contrast, levels were low and stable in other connective tissue diseases. Levels of TNF-alpha were low in patients with rheumatoid arthritis and high in patients with other connective tissue diseases, but without circadian rhythm. After treatment with prednisolone, levels of serum IL-6 decreased significantly, but the circadian rhythm remained. CONCLUSIONS--The circadian rhythm of circulating IL-6 might correspond to the circadian rhythm of symptoms in rheumatoid arthritis. The diurnal variation of IL-6, and possibly other cytokines, might explain the conflicting results previously reported on the inter-relationship between circulating IL-6 levels and disease activity in rheumatoid arthritis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-90243 (URN)7944637 (PubMedID)
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2017-12-14Bibliographically approved
2. Monocyte activation in rheumatoid arthritis: increased integrin, Fc gamma and complement receptor expression, and the effect of glucocorticoids
Open this publication in new window or tab >>Monocyte activation in rheumatoid arthritis: increased integrin, Fc gamma and complement receptor expression, and the effect of glucocorticoids
1999 In: Clinical and Experimental Immunology, Vol. 115, p. 554-60Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90244 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
3. Concordant message of different inflammatory markers in patients with rheumatoid arthritis
Open this publication in new window or tab >>Concordant message of different inflammatory markers in patients with rheumatoid arthritis
1998 In: Upsala journal of Medical Sciences, Vol. 103, p. 35-42Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90245 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
4. Disease activity in rheumatoid arthritis: fibrinogen is superior to the erythrocyte sedimentation rate
Open this publication in new window or tab >>Disease activity in rheumatoid arthritis: fibrinogen is superior to the erythrocyte sedimentation rate
2002 In: Scandinavian Journal of Clinical and Laboratory Investigations, Vol. 62, p. 315-20Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90246 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
5. The timing of glucocorticoid administration in rheumatoid arthritis
Open this publication in new window or tab >>The timing of glucocorticoid administration in rheumatoid arthritis
1997 In: Annals of the Rheumatic Diseases, Vol. 56, p. 27-31Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90247 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
6. Simple function tests, but not the modified HAQ, correlate with radiological joint damage in rheumatoid arthritis
Open this publication in new window or tab >>Simple function tests, but not the modified HAQ, correlate with radiological joint damage in rheumatoid arthritis
2002 In: Scandinavian Journal of Rheumatology, Vol. 31, p. 146-50Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90248 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved

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