Original ArticleInflammatory markers in patients with rheumatoid arthritis
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disorder that is characterised by polyarthritis with often progressive joint damage and disability, immunological abnormalities, systemic inflammation, increased co-morbidity, and premature mortality. It affects 1% of the adult population worldwide and also occurs among one in a thousand children as juvenile RA. RA is much more common in women and affects women 2–3 times more frequently than men, and during pregnancy 70% of women suffering from RA experience remission, with flare-ups after birth.1 The aetiology of RA is not known, but it is classified as one of the autoimmune diseases.2 It is associated with reduced life expectancy and a major cause of chronic disability and handicap, and conditions become more dangerous with time. Many studies have shown that advance therapy including the use of early, aggressive therapy, and the introduction of anti-cytokines agent have improved patient's quality of life, eased clinical symptoms, retarded the progression of joint destruction, and delayed disability.3
Inflammatory processes play a pivotal role in the pathogenesis of RA. Markers of inflammation such as C-reactive protein (CRP), interleukin (IL)-6, tumour necrosis factor (TNF)-α and anti-inflammatory marker IL-10 are highly expressed in synovium fluid and serum of arthritic patients and play an important role in the pathophysiology of RA. CRP is an acute-phase protein produced by hepatocytes, upon stimulation by the cytokines IL-1, IL-6 and TNF-α, during an acute-phase response.4, 5 CRP is a general marker of systemic inflammation and is elevated in patients with RA. Some studies reported a higher frequency of increased CRP concentrations in serum samples of RA patients before the onset of RA.6
In RA, several cytokines are involved in almost all aspects of articular inflammation and destruction.7 Increased levels of pro-inflammatory cytokines lead to the proliferation of synovial tissue, and thereby cause damage in the articular cartilage and bone destruction in the adjacent area. Anti-inflammatory cytokines can also be found in the affected joints, and it has been postulated that chronic synovitis may reflect an imbalance in pro- and anti-inflammatory cytokines production in RA. IL-6 is the most abundantly expressed cytokine in RA patients with biological activities that include regulation of immune response, inflammation, and haematopoiesis. IL-6 stimulates the secretion of immunoglobulin by plasmacytes, activates and promotes the proliferation of T and B cells (thus it is involved in the production of the rheumatoid factor), induces synthesis of acute-phase proteins such as CRP, fibrinogen, haptoglobin and serum amyloid-A, regulates the proliferation and differentiation of osteoclasts, and induces bone resorption.8
TNF-α is one of the pivotal pro-inflammatory cytokines responsible for inflammation and joint destruction in RA. TNF-α and its two receptors (p55 and p75 TNFR) are readily detected in both synovial fluid and serum of patients with RA. The severity of this disease is correlated with the concentration of TNF-α in RA patients.9 TNF-α is a potent stimulator of mesenchymal cells, such as synovial fibroblasts, osteoclasts, and chondrocytes that release tissue-destroying matrix metalloproteinases. TNF-α also inhibits the production of tissue inhibitors of metalloproteinases by synovial fibroblasts. These dual actions are thought to lead to joint damage. Although, TNF-α and IL-6 have overlapping and synergic actions, some of the effects of these two cytokines are regulated by distinct mechanisms.10 IL-10 is a potent immunosuppressive and anti-inflammatory cytokine, produced as a part of the homeostatic response to infection and inflammation, and plays a critical role in limiting the duration and intensity of immune and inflammatory reactions. As an anti-inflammatory cytokine, IL-10 has been shown to inhibit the synthesis of pro-inflammatory cytokines.
In the present study, we have screened 110 RA cases attending the Rheumatology OPD of a tertiary care hospital in Delhi, India. Acute phase protein hs-CRP, pro-inflammatory markers IL-6 and TNF-α and anti-inflammatory marker IL-10 were estimated in the serum of RA patients to rule out the levels of these biomarkers during active RA and compared them with healthy controls, and then investigated the correlation between serum levels of these inflammatory markers with the disease activity score 28 (DAS28) in the patient group.
Section snippets
Methods
The present study was carried out on 110 RA patients, fulfilling the 1987 revised criteria of the American College of Rheumatology (formerly, the American Rheumatism Association).11 All cases were selected from the Rheumatology Department of a tertiary care hospital in Delhi, India, under the guidance of a specialist rheumatologist. All patients had active RA (>3 swollen and >3 tender joints). Some of them had evidence of erosive disease on X-rays of hands or feet. Disease activity in RA
Results
The demographic and clinical data of the study groups are shown in Table 1. The mean age of the 110 patients with RA was 46.71 ± 7.12 years and the patient group was comprised of 30 males and 80 females. The mean value of morning stiffness was 85 ± 41.75 min. The mean disease duration of the patients was 58.3 ± 19.88 months. The mean DAS28 of RA patients was 4.13 ± 1.77. Fifteen of the 110 patients had a family history of RA or other types of arthritis, and 16 had a former fracture. RA is closely
Discussion
The results of our study confirm the observation of previous studies that the serum concentrations of inflammatory markers are elevated in the majority of patients with RA. RA is characterised by chronic inflammation and hypertrophy of the synovial membranes. Inflammation of the joints occurs in response to production of growth factors, cytokines, and chemokines by many different types of cells present in synovium and cartilage, in addition to infiltrating cells from the peripheral blood.12 In
Conflict of interest
None of the authors have a competing interest to disclose.
Funding statement
No funding was received for this study.
Confidentiality of data
The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.
Right to privacy and informed consent
The authors have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.
Protection of human and animal subjects
The authors declare that no experiments were
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