Subclinical atherosclerosis and related cytokines in polymyalgia rheumatica patients
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Original Article
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4 March 2026

Subclinical atherosclerosis and related cytokines in polymyalgia rheumatica patients

J Turk Soc Rheumatol. Published online 4 March 2026.
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No information available
Received Date: 06.10.2025
Accepted Date: 18.02.2026
E-Pub Date: 04.03.2026
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Abstract

Objective

This study aimed to evaluate subclinical atherosclerosis in patients with polymyalgia rheumatica (PMR) using carotid intima-media thickness (CIMT) and plaque assessment, and to investigate the potential association between PMR and inflammatory [interleukin (IL)-6, IL-8, IL-32, interferon (IFN)-γ, pentraxin-3 (PTX-3)] and anti-inflammatory (IL-5, IL-33, adiponectin) levels.

Methods

Between April 2011 and June 2012, thirty-three patients with PMR and twenty-eight healthy controls were enrolled. Clinical data, atherosclerotic risk factors, and biochemical parameters were recorded. Serum levels of IL-5, IL-6, IL-8, IL-32, IL-33, IFN-γ, adiponectin, and PTX-3 were measured using enzyme-linked immunosorbent assay. CIMT and plaque presence were evaluated by high-resolution ultrasonography.

Results

The mean age of the PMR group was 66.3±9.6 years and of the controls 62.5±5.1 years (p=0.103). No significant differences were observed regarding atherosclerotic risk factors. IL-5 levels were significantly higher in PMR patients compared to controls (167.7±16.6 vs. 155±18.3 pg/mL; p=0.009). PTX-3 levels were also significantly higher in the PMR group [433 (227.5-1059.5) vs. 347.3 (251-697.5) pg/mL; p=0.008]. No significant differences were detected for IL-6, IL-8, IL-32, IL-33, IFN-γ, or adiponectin levels between PMR and control groups. Mean CIMT (0.749±0.101 vs. 0.715±0.055 mm; p=0.270) and carotid plaque presence (20.7% vs. 4.2%; p=0.108) were not significantly different between groups.

Conclusion

This is the first study which has been demonstrated significantly elevated IL-5 levels in patients with PMR. Increased PTX-3 levels may indicate the presence of subclinical vascular inflammation. However, the absence of significant differences in CIMT and plaque presence suggests a possible influence of corticosteroid therapy on vascular parameters. These findings highlight a potential role of IL-5 in PMR pathogenesis, warranting further large-scale investigations.

Keywords:
Polimyalgia romatica, cytokines, carotis intima media, aterosclerosis

References

1
Raheel S, Shbeeb I, Crowson CS, Matteson EL. Epidemiology of polymyalgia rheumatica 2000-2014 and examination of incidence and survival trends over 45 years: a population-based study. Arthritis Care Res (Hoboken). 2017;69:1282-5.
2
Noltorp S, Svensson B. High incidence of polymyalgia rheumatica and giant cell arteritis in a Swedish community. Clin Exp Rheumatol. 1991;9:351-5.
3
Smeeth L, Cook C, Hall AJ. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. Ann Rheum Dis. 2006;65:1093-8.
4
Boesen P, Sørensen SF. Giant cell arteritis, temporal arteritis, and polymyalgia rheumatica in a Danish county. A prospective investigation, 1982-1985. Arthritis Rheum. 1987;30:294-9.
5
Schaufelberger C, Bengtsson BA, Andersson R. Epidemiology and mortality in 220 patients with polymyalgia rheumatica. Br J Rheumatol. 1995;34:261-4.
6
González-Gay MA, García-Porrúa C. Systemic vasculitis in adults in northwestern Spain, 1988-1997. Clinical and epidemiologic aspects. Medicine (Baltimore). 1999;78:292-308.
7
Pamuk ON, Dönmez S, Karahan B, Pamuk GE, Cakir N. Giant cell arteritis and polymyalgia rheumatica in northwestern Turkey: clinical features and epidemiological data. Clin Exp Rheumatol. 2009;27:830-3.
8
Sobrero A, Paolino S, Hysa E, et al. Seasonal onset of polymyalgia rheumatica: correlations with the pattern of clinical presentation, disease severity and outcome in 383 patients from a single centre. Clin Exp Rheumatol. 2021;39:564-9.
9
Meliconi R, Pulsatelli L, Uguccioni M, et al. Leukocyte infiltration in synovial tissue from the shoulder of patients with polymyalgia rheumatica. Quantitative analysis and influence of corticosteroid treatment. Arthritis Rheum. 1996;39:1199-207.
10
Pulsatelli L, Boiardi L, Pignotti E, et al. Serum interleukin-6 receptor in polymyalgia rheumatica: a potential marker of relapse/recurrence risk. Arthritis Rheum. 2008;59:1147-54.
11
Cantini F, Salvarani C, Olivieri I, et al. Shoulder ultrasonography in the diagnosis of polymyalgia rheumatica: a case-control study. J Rheumatol. 2001;28:1049-55.
12
McGonagle D, Pease C, Marzo-Ortega H, O’Connor P, Gibbon W, Emery P. Comparison of extracapsular changes by magnetic resonance imaging in patients with rheumatoid arthritis and polymyalgia rheumatica. J Rheumatol. 2001;28:1837-41.
13
Salvarani C, Gabriel SE, O’Fallon WM, Hunder GG. Epidemiology of polymyalgia rheumatica in Olmsted County, Minnesota, 1970-1991. Arthritis Rheum. 1995;38:369-73.
14
Healey LA. Long-term follow-up of polymyalgia rheumatica: evidence for synovitis. Semin Arthritis Rheum. 1984;13:322-8.
15
Dasgupta B, Cimmino MA, Maradit-Kremers H, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71:484-92.
16
Dejaco C, Singh YP, Perel P, et al. 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2015;74:1799-807.
17
Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135-43.
18
Matsuura E, Kobayashi K, Lopez LR. Atherosclerosis in autoimmune diseases. Curr Rheumatol Rep. 2009;11:61-9.
19
Tokgözoğlu L. Ateroskleroz ve enflamasyonun rolü [Atherosclerosis and the role of inflammation]. Turk Kardiyol Dern Ars. 2009;37(Suppl 4):1-6.
20
Shindo A, Tanemura H, Yata K, et al. Inflammatory biomarkers in atherosclerosis: pentraxin 3 can become a novel marker of plaque vulnerability. PLoS One. 2014;9:e100045.
21
Feijóo-Bandín S, Aragón-Herrera A, Moraña-Fernández S, et al. Adipokines and inflammation: focus on cardiovascular diseases. Int J Mol Sci. 2020;21:7711.
22
Heinhuis B, Popa CD, van Tits BL, et al. Towards a role of interleukin-32 in atherosclerosis. Cytokine. 2013;64:433-40.
23
Miller AM, Xu D, Asquith DL, et al. IL-33 reduces the development of atherosclerosis. J Exp Med. 2008;205:339-46.
24
Binder CJ, Hartvigsen K, Chang MK, et al. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J Clin Invest. 2004;114:427-37.
25
Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis. Ann Intern Med. 1994;121:484-91.
26
Cutolo M, Straub RH, Foppiani L, et al. Adrenal gland hypofunction in active polymyalgia rheumatica. Effect of glucocorticoid treatment on adrenal hormones and interleukin 6. J Rheumatol. 2002;29:748-56.
27
Roche NE, Fulbright JW, Wagner AD, Hunder GG, Goronzy JJ, Weyand CM. Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum. 1993;36:1286-94.
28
Ramirez GA, Rovere-Querini P, Blasi M, et al. PTX3 intercepts vascular inflammation in systemic immune-mediated diseases. Front Immunol. 2019;10:1135.
29
Pulsatelli L, Peri G, Macchioni P, et al. Serum levels of long pentraxin PTX3 in patients with polymyalgia rheumatica. Clin Exp Rheumatol. 2010;28:756-8.
30
Mahanty S, Nutman TB. The biology of interleukin-5 and its receptor. Cancer Invest. 1993;11:624-34.
31
Bischoff SC, Brunner T, De Weck AL, Dahinden CA. Interleukin 5 modifies histamine release and leukotriene generation by human basophils in response to diverse agonists. J Exp Med. 1990;172:1577-82.
32
Álvarez-Rodríguez L, López-Hoyos M, Calvo-Alén J, Aurrecoechea E, Villa I, Martínez-Taboada VM. Phagocyte dysfunction in polymyalgia rheumatica and other age-related, chronic, inflammatory conditions. J Leukoc Biol. 2013;94:1071-8.
33
Galbo H, Kall L. Circadian variations in clinical symptoms and concentrations of inflammatory cytokines, melatonin, and cortisol in polymyalgia rheumatica before and during prednisolone treatment: a controlled, observational, clinical experimental study. Arthritis Res Ther. 2016;18:174.
34
Heinhuis B, Koenders MI, van de Loo FA, Netea MG, van den Berg WB, Joosten LA. Inflammation-dependent secretion and splicing of IL-32{gamma} in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2011;108:4962-7.
35
Miller AM. Role of IL-33 in inflammation and disease. J Inflamm (Lond). 2011;8:22.
36
Palmer G, Talabot-Ayer D, Lamacchia C, et al. Inhibition of interleukin-33 signaling attenuates the severity of experimental arthritis. Arthritis Rheum. 2009;60:738-49.
37
Ciccia F, Alessandro R, Rizzo A, et al. Expression of interleukin-32 in the inflamed arteries of patients with giant cell arteritis. Arthritis Rheum. 2011;63:2097-104.
38
Ciccia F, Alessandro R, Rizzo A, et al. IL-33 is overexpressed in the inflamed arteries of patients with giant cell arteritis. Ann Rheum Dis. 2013;72:258-64.
39
Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995;270:26746-9.
40
Scrivo R, Silvestri V, Ciciarello F, et al. An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica. Sci Rep. 2020;10:11407.
41
Kaser S, Tatarczyk T, Stadlmayr A, et al. Effect of obesity and insulin sensitivity on adiponectin isoform distribution. Eur J Clin Invest. 2008;38:827-34.
42
Tau G, Rothman P. Biologic functions of the IFN-gamma receptors. Allergy. 1999;54:1233-51.
43
Floris A, Piga M, Cauli A, Salvarani C, Mathieu A. Polymyalgia rheumatica: an autoinflammatory disorder? RMD Open. 2018;4:e000694.
44
Schillaci G, Bartoloni E, Pucci G, et al. Aortic stiffness is increased in polymyalgia rheumatica and improves after steroid treatment. Ann Rheum Dis. 2012;71:1151-6.