The Relation of Interleukin 17 (IL-17) and IL-23 to Th1/Th2 Cytokines and Disease Activity in Systemic Lupus Erythematosus
ABSTRACT Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic lupus erythematosus (SLE), but its relation to disease activity has not been well characterized. We examined the relation between serum levels of Th17 (IL-17, IL-23), Th1 (IL-12, interferon-γ), Th2 (IL-10, IL-6, IL-4) cytokines and disease activity in patients with SLE.
Serum cytokines were measured by enzyme linked immunosorbent assays. Disease activity was determined by SLE disease activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels.
Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher serum IL-23 level was found in patients with active disease with cutaneous manifestations (p = 0.004) and serositis (p = 0.04) compared to those without. Serum IL-17 level above the detection limit was more frequently found in patients who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001) compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable between these 3 groups of patients and were not related to SLEDAI, glomerular filtration rate, activity or chronicity score and ISN/RPS criteria class among patients with active lupus nephritis. There was no significant correlation between serum IL-17/IL-23 and Th1 or Th2 cytokine levels.
SLE patients had higher serum IL-17 levels than healthy controls. Elevated serum IL-23 was found in patients with inflammatory manifestations including cutaneous involvement and serositis. The lack of correlation between Th17, Th1, and Th2 cytokines suggested independent regulatory mechanisms for these cytokines.
- SourceAvailable from: Wayel H Abdulahad
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- "The IL-21/IL-21R pathway seems to play an important role in the homeostasis of T-cells, in particular in the differentiation of naïve T-cells towards Th17 cells. These cells have been identified to be key mediators in autoimmune diseases such as SLE [13-15]. Additionally, Th17 cells have been shown to be a source of IL-21 . "
ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients. Peripheral blood of 34 SLE patients and 18 healthy controls (HC) was stimulated with phorbol myristate acetate (PMA) and calcium ionophore (Ca-Io). Percentages of IL-21- and IL-17A expressing T-cells were analysed by flow cytometry. The expression levels of the transcription factors B-cell lymphoma-6 (BCL-6) and factors retinoid-related orphan receptor (ROR-γt) were assessed in T-cells by real-time RT-PCR and flow cytometry. Additionally, IL-21 receptor (IL-21R) expression on B- and T-cells of patients and HC was analyzed. Significantly increased percentages of IL-21 expressing CD4+ T-cells and CD8+ T-cells were found in SLE patients as compared to HC. The percentages of IL-21+ CD4+ T-cells and CD8+ T-cells correlated significantly with the percentages of IL-17A+ CD4+ T-cells and CD8+ T-cells, respectively. The relative expression of BCL-6 and ROR-γt did not differ between SLE patients and HC. IL-21R expression occurred mainly on B-cells and was not different comparing SLE patients and HC. This study demonstrates an increased proportion of IL-21+ T-cells in SLE patients correlating with the proportion of IL-17+ T-cells. This suggests a pivotal role of IL-21 in the pathogenesis of SLE.Arthritis research & therapy 09/2011; 13(5):R157. DOI:10.1186/ar3474 · 3.75 Impact Factor
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- "They provide immediate immunological protection by producing antimicrobial and acute phase response proteins against a variety of pathogens, specifically Propionibacterium acnes, Citrobacter rodentium, Klebsiella pneumoniae, Bacteroides spp., Staphylococcus aureus , acid-fast Mycobacterium tuberculosis, and fungi infection such as Candida albicans  . Most importantly, having the potential to upregulate the expression of specifics matrix metalloproteinases (MMPs) such as MMP-1, MMP-3, MMP-9, MMP-13, IL-17A, and IL- 17F have been shown to be tissue-damaging cytokines and are intimately involved in autoimmune diseases, for example, Crohn's disease  , EAE , collagen-induced arthritis (CIA) , Sjögren's syndrome (SjS)   and SLE which will be later discussed      . However, a recent study by Ishigame et al.  suggested that there are differential roles for IL-17A and IL-17F in autoimmune responses, in which IL-17F played a minimal role in the pathogenesis of delayed-type and contact hypersensitivities, EAE, CIA, and arthritis in animal models. "
ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a multifaceted range of symptoms affecting almost every organ system. The prototypical pathology of SLE involves the production of antinuclear antibodies and the deposition of immune complexes in basement membranes throughout the body where they induce inflammatory responses. The genetic and environmental etiologies of this process are being intensively sought, and recently, T H 17 cells have been implicated in the pathogenesis of SLE. T H 17 cells are CD4+ memory T cells that behave as both helper and effector cell populations functioning through their signature IL-17 cytokines. Their differentiation is distinct to either the T H 1 or T H 2 cell lineage, but strongly influences development of adaptive responses, including autoimmunity. This paper details the biological functions and regulation of T H 17 cells, followed by an update of their expanding role in SLE.03/2011; 2011(2090-1984):810649. DOI:10.1155/2011/810649
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- "Atherosclerotic-prone mice have reduced plaque burden when transplanted with bone marrow deficient in the IL-17 receptor . SLE patients have elevated levels of IL-17 and Th17 cells are expanded in SLE and can induce endothelial adhesion molecule upregulation [50,51]. Thus, there is a theoretical role for Th17 T cells and IL-17 in the upregulation of inflammatory mediators and adhesion molecules that contribute to CVD in SLE. "
ABSTRACT: Patients with systemic lupus erythematosus have up to a 50-fold increased risk of developing atherosclerotic cardiovascular disease. Recent advances in the etiology of vascular damage in this disease stress the interplay of lupus-specific inflammatory factors with traditional cardiac risk factors, leading to increased endothelial damage. This review analyzes the putative role that immune dysregulation and lupus-specific factors may play in the pathogenesis of premature vascular damage in this disease. The potential role of various cytokines, in particular type I interferons, in the development of accelerated atherosclerosis is examined. Potential therapeutic targets are discussed.Arthritis research & therapy 02/2011; 13(1):203. DOI:10.1186/ar3264 · 3.75 Impact Factor