Serum cytokines in juvenile rheumatoid arthritis: correlation with conventional inflammation parameters and clinical subtypes

Abstract

Objective. To examine the usefulness of determining extended serum cytokine profiles in patients with juvenile rheumatoid arthritis (JRA), for the purpose of improving differential diagnosis and monitoring disease activity. Methods. In a 2‐year prospective study, serum levels of interleukin‐1β (IL‐1β), soluble IL‐2 receptor (sIL‐2R), IL‐6, IL‐8, tumor necrosis factor α (TNFα), and the p55 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme‐linked immunosorbent assay in 40 patients with JRA, 13 patients with postinfectious arthropathies, and 30 healthy controls. The data were compared with conventional parameters of inflammation, such as C‐reactive protein (CRP), iron and hemoglobin levels, erythrocyte sedimentation rate (ESR), white blood cell (WBC) counts, and platelet counts. WBC subsets were analyzed by flow cytofluorometry. Results. At the first visit and at the peak of inflammatory activity according to CRP levels and/or ESR, serum levels of sIL‐2R, IL‐6, and sTNFR in JRA patients correlated significantly with conventional inflammation indicators, whereas IL‐1β, IL‐8, and TNFα did not. No changes in leukocyte subset distribution were noted. Among the different clinical subtypes of JRA, sIL‐2R, IL‐6, and sTNFR values at the time of the initial visit showed a pattern similar to CRP, whereby patients with systemic disease exhibited by far the highest values. TNFα and IL‐1β were variably elevated in certain JRA subtypes. Patients with postinfectious arthropathies showed elevated levels of CRP, sIL‐2R, TNFα, and sTNFR, which did not differ significantly from levels in the various JRA subtypes with the exception of systemic disease. Detailed analysis of types I and II pauciarticular JRA revealed that levels of CRP, IL‐1β, and TNFα were elevated in patients with type I disease. While these parameters were invariably normal in patients with type II disease, sTNFR and sIL‐2R were still found to be significantly elevated. Followup studies suggested that persistently high sTNFR values are a better indicator of JRA activity than are measurements of other cytokines or CRP. Conclusion. JRA is associated with significant and consistent changes in serum levels of inflammatory cytokines and soluble receptors. For the clinical monitoring of JRA, determination of levels of sTNFR, and to some extent sIL‐2R, may be particularly useful, since these determinations yield information about subtype and/or activity of disease that is not available from conventional parameters of inflammation.

Distinct Cytokine Profiles in Patients with Oligoarticular Juvenile Idiopathic Arthritis after <i>in</i> <i>Vitro</i> Blockade of T Cells by Cyclosporine and Abatacept

“…TNF-α is regarded as a crucial cytokine in JIA-pathogenesis [20] [34] [35]. Consistent with this hypothesis we found a distinct increase in concentration after PHA stimulation which was considerably higher in the group of patients compared to healthy control subjects.…”

Critical Paracrine Interactions Between TNF-α and IL-10 Regulate Lipopolysaccharide-Stimulated Human Choriodecidual Cytokine and Prostaglandin E2 Production

“…TNF-␣ is a potent proinflammatory mediator and has been implicated as the primary cause of many immunopathologies ranging from arthritis (42)(43)(44) to septic shock (45,46), in addition to preterm labor (47). Mice treated with Abs or antagonists to TNF-␣ are subsequently protected from LPS-induced death (45,48,49).…”

Novel IL-6 haplotypes and disease association

“…1,2 This is in keeping with clinical findings that high serum IL-6 correlates with active disease and fever. [3][4][5] Since our first report, this variant has been associated with numerous diseases including type I and II diabetes mellitus, 6,7 SLE, 8 Sjögren's syndrome, 9 bone density and osteoporosis, [10][11][12] Alzheimer disease 13 and coronary heart disease. [14][15][16] The candidate gene approach has been widely used to analyse possible associations between genetic variants and autoimmune and inflammatory diseases, with the selection of genes by investigators based on a priori knowledge of disease pathogenesis and phenotypes.…”