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Interleukin-1 receptor antagonist is associated with both lipid metabolism and inflammation in rheumatoid arthritis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
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2007 (English)In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 25, no 4, 617-620 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: There is a relationship between cardiovascular morbidity, inflammatory activity, and changes in the lipid profile in rheumatoid arthritis (RA), although the mechanisms are not fully elaborated. Recent know-ledge that white adipose tissue (WAT) is a producer of immunologically and metabolically active substances gives another perspective to study.

OBJECTIVE: To evaluate the relationship between interleukin-1 receptor antagonist (IL-1Ra) and variables associated with WAT and inflammation in RA.

METHODS: Anthropometric, inflammatory and metabolic variables were assessed in 23 women with RA and 23 matched controls. Spearman, partial correlation and factor analyses were performed.

RESULTS: Inflammatory markers were increased in patients. In both groups, IL-1Ra correlated with leptin independent of age and BMI. IL-1Ra also correlated with haptoglobin and apolipoprotein (Apo) B in patients and with soluble TNF receptor (sTNFR) 1 in controls. In factor analysis, three latent factors were identified among patients. The first loaded on IL-1Ra, leptin, BMI, ApoB and body fat content (BF%), the second loaded on IL1-Ra and sTNF-receptors and the third showed inverse loadings on ApoA-I together with loadings on ESR, haptoglobin, orosomucoid, BF% and BMI.

CONCLUSION: IL-1Ra was associated with markers of inflammation and with fat-related factors in RA patients, suggesting a dualistic relationship of IL-1Ra in RA. IL-1Ra correlated independently with leptin in both patients and controls, indicating a relationship between inflammation and leptin.

Place, publisher, year, edition, pages
2007. Vol. 25, no 4, 617-620 p.
National Category
Rheumatology and Autoimmunity
URN: urn:nbn:se:umu:diva-16984PubMedID: 17888220OAI: diva2:156657
Available from: 2007-10-25 Created: 2007-10-25 Last updated: 2012-08-17Bibliographically approved
In thesis
1. Aspects on inflammation and cardiovascular comorbidity in rheumatoid arthritis
Open this publication in new window or tab >>Aspects on inflammation and cardiovascular comorbidity in rheumatoid arthritis
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is an increased risk for cardiovascular (CV) comorbidity among patients with rheumatoid arthritis (RA), with premature atherosclerosis, and a higher incidence of CV events, compared with the general population. Disease related factors add to the CV risk, and interact with the traditional CV risk factors. The underlying mechanism for this is not completely understood. In active RA there is a loss of muscle mass and an increase in body fat content. Production of cytokines, i.e., adipokines, in the adipose tissue could link the inflammation with the CV system. Control of the inflammation has been suggested to modify the CV risk in RA, and the recently introduced biological drugs, such as the tumor necrosis factor inhibitors (TNFi), have opened up new treatment opportunities. The aim of this thesis was to evaluate aspects of the interaction between inflammation and CV comorbidity in RA using biochemical and epidemiological methods.


In the first two studies, patients with established RA were examined for clinical disease activity, and blood samples were analysed for cytokines and adipokines using ELISAs and multiplex technology. In Study I (n RA=23) anthropometric measurements were assessed and in Study II (n RA=51) measurements of intima-media thickness (IMT), and endothelial function (FMD). From a subgroup of patients (Study II, n RA=13) samples of abdominal subcutaneous adipose tissue (SAT) were analysed for content of adipokines. In study III and IV associations between treatment with TNFi and acute coronary syndromes (ACS) were analysed using data from the Swedish Rheumatology Register; in Study III regarding early RA (n TNFi exposed=1,271, n bionaïve RA=4,729), and in Study IV comprising patients with RA of all stages (n TNFi exposed=7,213, n bionaïve RA=17,769) and with a matched general population comparator cohort (n=32,161). Associations between response to TNFi therapy and risk for ACS in the early RA cohort were evaluated in a nested case-control design (cases n=24, controls n=81).


Serum levels of the cytokines/adipokines interleukin-1 receptor antagonist (IL-1Ra), IL-6, osteopontin, visfatin and TNF were increased in patients compared with controls (p≤0.001-0.036). The amount of TNF receptor II extracted from SAT was greater in patients (p=0.006). The serum (s-) levels of IL-1Ra correlated with s-leptin (r=0.71, p≤0.001) and s-haptoglobin in RA patients (r=0.56, p≤0.01). The result from a factor analysis indicated IL-1Ra to be associated with both adipose tissue and inflammation. Levels of s-visfatin (p=0.019) and s-IL-1Ra (p=0.023), respectively, were positively associated with IMT independently of inflammatory activity and CV risk factors. PAI-1 and MCP-1 extracted from SAT showed inverse associations with IMT.

Patients with RA, whether exposed to TNFi or bio-naïve, had a doubled risk for ACS compared with the general population; HR 2.09 (95%CI 1.58-2.76) and 1.80 (1.49-2.17), respectively. No significant associations between risk for ACS and TNFi exposure were detected after adjustments; HR 0.80 (0.52-1.24) in early RA and HR 1.08 (0.82-1.41) in RA of any duration. Furthermore, no association between the risk for ACS and response to TNFi treatment in patients with early RA was observed, OR 1.5 (0.3-6.9).


The results indicate that cytokines/adipokines may have a role in the development of atherosclerosis in RA patients. A continuing increase in the risk of ACS in RA compared with the general population, despite modern therapeutic strategies, was noted. Neither exposure nor response to treatment with TNFi was associated with any modification of the risk for ACS.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2012. 102 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1514
rheumatoid arthritis, co-morbidity, cardiovascular disease, atherosclerosis, acute coronary syndromes, adipokines, adipose tissue, tumor necrosis factor inhibition
National Category
Rheumatology and Autoimmunity
urn:nbn:se:umu:diva-57702 (URN)978-91-7459-461-4 (ISBN)
Public defence
2012-09-07, sal E04, Biomedicinhuset, byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2012-08-17 Created: 2012-08-09 Last updated: 2012-08-17Bibliographically approved

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Ljung, LottaOlsson, TommyWållberg-Jonsson, SolveigSöderberg, StefanRantapää-Dahlqvist, Solbritt
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