Aktuelle Rheumatologie 2017; 42(04): 323-328
DOI: 10.1055/s-0035-1564141
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Serum Levels of IL-17, IL-6, TNF-α and Disease Activity in Patients with Rheumatoid Arthritis

Serumspiegel von IL-17, IL-6 und TNF-α und Krankheitsaktivität bei Patienten mit rheumatoider Arthritis
M. S. Beyazal
1   Department of Physical Medicine and Rehabilitation, Reccep Tayyip Erdoğan University, Rize, Turkey
,
G. Devrimsel
2   Physical Medicine and Rehabilitation, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
,
M. C. Cüre
3   Department of Biochemistry, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
,
A. K. Türkyılmaz
4   Department of Physical Medicine and Rehabilitation, School of Medicine, Reccep Tayyip Erdoğan University, Rize, Turkey
,
E. Çapkın
5   Department of Physical Medicine and Rehabilitation, Karadeniz Technical University, Trabzon, Turkey
,
M. Karkucak
6   Department of Physical Medicine and Rehabilitation, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
› Author Affiliations
Further Information

Publication History

Publication Date:
17 May 2016 (online)

Abstract

Objective: The aim of this study was to evaluate serum levels of interleukin (IL)-17, IL-6, and tumor necrosis factor alpha (TNF-α) in RA patients and to assess the correlation of these cytokines with clinical and laboratory parameters.

Materials and Methods: 48 patients with RA and 35 healthy volunteers were enrolled in the study. Disease activity was determined by disease activity score (DAS28) in patients with RA. Patients with RA were categorized as mild (DAS28≤3.2), moderate (3.2<DAS28≤5.1), and severe (5.1<DAS28) according to DAS28. The serum levels of IL-17, IL-6 and TNF-α cytokines were measured by enzyme-linked immuno sorbent assay.

Results: The mean serum IL-17 and TNF-α levels did not differ between RA patients and controls (P>0.05). Serum IL-6 levels were significantly elevated in RA patients compared with controls (P<0.001). The increasing trend in mean serum IL-6 levels across group with mild, moderate, and severe disease activity was significant (P<0.001, respectively). In RA patients, serum IL-6 concentrations were significantly correlated with ESR, CRP, DAS28, and VAS (r=0.371, P=0.009; r=0.519, P<0.001; r=0.536, P<0.001; r=0.539, P<0.001, respectively). Also, Serum IL-17 concentrations demonstrated significant correlations with ESR, CRP, but not DAS28 (r=0.349, P=0.015; r=0.299, P=0.039; r=0.274, P=0.060, respectively). Serum TNF-α showed no significant correlation with disease activity indices.

Conclusions: This study showed that patients with RA had significantly increased cytokine level for IL-6, but not IL-17 and TNF-α and high level of serum IL-6 cytokine was associated with disease activity. However, further follow-up studies involving large samples are required to clarify precise role of these cytokines in disease development and progress.

Zusammenfassung

Zielsetzung: Ziel dieser Studie war es, bei RA-Patienten die Serumspiegel von Interleukin (IL)-17, IL-6 und Tumornekrosefaktor-alpha (TNF-α) zu untersuchen und die Korrelation dieser Zytokine mit klinischen und laborchemischen Parametern zu beurteilen.

Material und Methoden: Es wurden 48 Patienten mit RA und 35 gesunde Probanden in die Studie aufgenommen. Bei den Patienten mit RA wurde anhand des Disease Activity Score (DAS28) die Krankheitsaktivität ermittelt. Diese wurde gemäß DAS28 als leicht (DAS28≤3,2), mittelschwer (3,2<DAS28≤5,1) und schwer (5,1<DAS28) eingestuft. Die Serumspiegel der Zytokine IL-17, IL-6 und TNF-α wurden mithilfe eines ELISA [Enzyme-linked Immunosorbent Assay] bestimmt.

Ergebnisse: Bei den mittleren Serumspiegeln von IL-17 und TNF-α fand sich zwischen den RA-Patienten und den Kontrollen kein signifikanter Unterschied (p>0,05). Die Serumspiegel von IL-6 waren bei den RA-Patienten im Vergleich zu den Kontrollen signifikant erhöht (p<0,001). In allen Patientengruppen mit leichter, mittelschwerer und schwerer Krankheitsaktivität fand sich eine signifikante Tendenz zur Zunahme der mittleren Serumspiegel von IL-6 (jeweils p<0,001). Bei den RA-Patienten korrelierten die Serumkonzentrationen von IL-6 signifikant mit ESR, CRP, DAS28 und VAS (r=0,371, p=0,009; r=0,519, p<0,001; r=0,536, p<0,001 bzw. r=0,539, p<0,001). Darüber hinaus zeigten die Serumkonzentrationen von IL-17 eine signifikante Korrelation mit ESR und CRP, nicht aber nicht DAS28 (r=0,349, p=0,015; r=0,299, p=0,039 bzw. r=0,274, p=0,060). Die Serumspiegel von TNF-α zeigten keine signifikante Korrelation mit den Krankheitsaktivitätsindizes.

Schlussfolgerungen: Diese Studie zeigte, dass bei RA-Patienten der Zytokinspiegel von IL-6 signifikant erhöht war, der von IL-17 und TNF-α hingegen nicht. Außerdem ergab die Studie, dass der hohe Serumspiegel des Zytokins IL-6 mit der Krankheitsaktivität assoziiert war. Die genaue Funktion dieser Zytokine bei der Entwicklung und Progression der Erkrankung muss jedoch in weiteren Folgestudien mit großen Stichproben geklärt werden.

 
  • References

  • 1 Kelner H. Targeting interleukin-17 in patients with active rheumatoid arthritis: rationale and clinical potential. Ther Adv Musculoskel Dis 2013; 5: 141-152
  • 2 Horton SC, Walsh CA, Emery P. Established rheumatoid arthritis: rationale for best practice: physicians’ perspective of how to realize tight control in clinical practice. Best Pract Res Clin Rheumatol 2011; 25: 509-521
  • 3 Hitchon CA, Alex P, Erdile LB. et al. A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis. J Rheumatol 2004; 31: 2336-2346
  • 4 Mewar D, Wilson AG. Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors. Br J Pharmacol 2011; 162: 785-791
  • 5 Furst DE, Emery P. Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets. Rheumatology (Oxford) 2014; 53: 1560-1569
  • 6 Shahrara S, Pickens SR, Dorfleutner A. et al. IL-17 induces monocyte migration in rheumatoid arthritis. J Immunol 2009; 182: 3884-3891
  • 7 Keijsers RR, Joosten I, van Erp PE. et al. Cellular sources of IL-17 in psoriasis: a paradigm shift?. Exp Dermatol 2014; 23: 799-803
  • 8 Hueber AJ, Asquith DL, Miller AM. et al. Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol 2010; 184: 3336-3340
  • 9 Tang C, Chen S, Qian H. et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology 2012; 135: 112-124
  • 10 van den Berg W, Miossec P. IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 2009; 5: 549-553
  • 11 Suurmond J, Dorjée AL, Boon MR. et al. Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther 2011; 13: R150
  • 12 Metawi SA, Abbas D, Kamal MM. et al. Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. Clin Rheumatol 2011; 30: 1201-1207
  • 13 Arnett FC, Edworthy SM, Bloch DA. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-324
  • 14 Prevoo ML, van’t Hof MA, Kuper HH. et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 44-48
  • 15 Mrabet D, Laadhar L, Sahli H. et al. Synovial fluid and serum levels of IL-17, IL-23, and CCL-20 in rheumatoid arthritis and psoriatic arthritis: a Tunisian cross-sectional study. Rheumatol Int 2013; 33: 265-266
  • 16 Zhang L, Li YG, Li YH. et al. Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with anklosing spondylitis and rheumatoid arthritis. PLos one 2012; 7: e31000
  • 17 Roşu A, Mărgăritescu C, Stepan A. et al. IL-17 patterns in synovium, serum and synovial fluid from treatment-naive, early rheumatoid arthritis patients. Rom J Morphol Embryol 2012; 53: 73-80
  • 18 Pavloviv V, Dimic A, Milenkovic S. et al. Serum levels of IL-17, IL-4, INF gama in Serbian patients with early rheumatoid arthritis. J Res Med Sci 2014; 19: 18-22
  • 19 McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007; 7: 429-442
  • 20 Raza K, Falciani F, Curnow SJ. et al. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther 2005; 7: 784-795
  • 21 Kokkonen H, Söderström I, Rocklöv J. et al. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum 2010; 62: 383-391
  • 22 Gullick NJ, Abozaid HS, Jayaraj DM. et al. Enhanced and persistent levels of interleukin (IL)-17+ CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis. Clin Exp Immunol 2013; 174: 292-301
  • 23 Nishimoto N, Kishimoto T. Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2006; 2: 619-626
  • 24 Madhok R, Crillly A, Watson J. et al. Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis 1993; 52: 232-234
  • 25 Chung SJ, Kwon YJ, Park MC. et al. The correlation between increased serum concentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J 2011; 52: 113-120
  • 26 Saeki Y, Tanaka EK, Ohshima S. et al. Baseline anti-citrullinated peptide antibody (ACPA) titers and serum interleukin-6 (IL-6) levels possibly predict progression of bone destruction in early stages of rheumatoid arthritis. Rheumatol Int 2013; 33: 451-456
  • 27 Nishina N, Kaneko Y, Kameda H. et al. Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis: a potential biomarker for radiographic progression. Clin Rheumatol 2013; 32: 1661-1666