Th1/Th2 cytokine profile in childhood-onset systemic lupus erythematosus

Postal, Mariana; Peliçari, Karina de Oliveira; Sinicato, Nailú Angélica; Marini, Roberto; Costallat, Lílian Tereza Lavras; Appenzeller, Simone

doi:10.1016/j.cyto.2012.11.023

Cited by 49 publications

(44 citation statements)

References 77 publications

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“…In a Thai population, high serum levels of IL-10 and association with disease activity were reported in cSLE patients (21). In a population in southern Brazil, increased levels of IL-10 were associated with anti-dsDNA in cSLE (14 ). The majority of studies involving adult SLE patients also reported increased levels of IL-10, which were associated with disease activity and increased production of anti-dsDNA (22).…”

Section: Discussionmentioning

confidence: 99%

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

Cavalcanti

Santos

Mesquita

et al. 2017

Braz J Med Biol Res

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Childhood-onset systemic lupus erythematosus (cSLE) exhibits an aggressive clinical phenotype and severe complications. This could be due to a pro-inflammatory cytokine milieu. Therefore, we determined plasma levels of Th1 (IL-2, IFN-γ, TNF), Th2 (IL-4), Th17 (IL-17A, IL-6), and Treg (IL-10) cytokines in a cohort of cSLE patients and healthy controls, and we evaluated the association between these cytokines and disease activity. We conducted a cross-sectional study with 51 cSLE patients from two pediatric rheumatology services. Ten cSLE patients participated in a longitudinal follow-up study. Blood samples were collected from the same patient during active and inactive disease. Disease activity was evaluated according to SLE Disease Activity Index 2000 (SLEDAI-2K). Cytokines levels were measured by cytometric bead array technique. cSLE patients had higher IL-6 (P<0.001) and IL-10 (P<0.001) levels than healthy controls. Patients with active disease had higher IL-6 and IL-10 levels than patients with inactive disease (P=0.001 and P=0.014, respectively) and the control group (both P<0.001). IL-6 (P=0.022), IL-10 (P=0.013), and IL-17A (P=0.041) levels were significantly higher during active than inactive disease. Linear regression analysis revealed IL-6 (P=0.002, 95%CI=0.006-0.025) and IL-10 (P=0.01 95%CI=0.021-0.150) as independent factors for increased SLEDAI-2K. IL-6, IL-10, and IL-17A are candidate biomarkers for disease activity in cSLE patients. This is the first longitudinal study to support their pivotal role in the pathogenesis of the disease.

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Section: Discussionmentioning

confidence: 99%

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

Cavalcanti

Santos

Mesquita

et al. 2017

Braz J Med Biol Res

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“…Studies involving systemic lupus erythematosus (SLE) patients have reported increased numbers of Th17 cells in sera and in the biopsied tissue of individuals with kidney damage and lupus nephritis (LN) (4,5). Increased IL-17A levels have also been reported in the sera of SLE patient subsets, particularly those with LN (4)(5)(6). Furthermore, in lupus-prone mice, the over-expression of IL-17A and subsequent expansion of DN T cells in the tubulointerstitial space has been linked to the development of nephritis (4,(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 98%

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Raymond¹,

Ostli-Eilertsen²,

Griffiths³

et al. 2017

Eur J Rheumatol

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Objective: The interleukin 17 (IL-17) cytokine family is involved in a number of chronic inflammatory diseases. In spite of contradictory findings and a lack of causality in clinical studies, IL-17 inhibition for systemic lupus erythematosus (SLE) has regained attention as a potential therapeutic pathway, after demonstrating disease-modifying capabilities in ankylosing spondylitis. We investigated the clinical associations of interleukin 17 A (IL-17A) in patients with SLE.Material and Methods: A cross-sectional study was performed involving SLE patients (n=102; age: 49 years; 86% female) recruited from a regional registry. IL-17A levels were determined by immunoassay, disease activity by Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K), and cumulative damage by Systemic Lupus International Collaborative Clinics Damage Index (SDI) scores. Non-parametric techniques were used to examine the association between IL-17A and disease activity and autoantibody profiles were compared with healthy controls (n=31): principal component analysis (PCA) was used to determine the interplay of immune cells across disease states and damage development in SLE patients.Results: SLE patients had higher IgG levels, lower T-cell and B-cell counts, but median IL-17A levels did not differ from the controls (28.4 vs. 28.4 pg/mL, p=0.9). In SLE patients, IL-17A did not correlate with SLEDAI-2K or SDI, but was inversely related with age (correlation coefficients, Rs.=-0.29, p<0.05), systolic blood pressure (Rs.=-0.31, p<0.05), years of smoking (Rs.=-0.43, p<0.05), cumulative heart (Rs.=-0.22, p<0.05), and malignancy damage (Rs.=-0.18, p<0.05). Serological correlations for IL-17A existed with immunoglobulin G (IgG) levels (Rs.=0.21, p<0.05), high sensitivity C-reactive protein (hs-CRP) levels (Rs.=0.28, p<0.05), proteinuria (Rs.=0.64, p<0.05), and pre-albumin (Rs.=-0.22, p<0.05). Longitudinal data showed only modest fluctuation in IL-17A levels, independent of SLEDAI-2K. Conclusion:These results suggest that IL-17A, while participating in inflammation, may also serve a protective purpose in SLE patients.

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“…16-18 (ii) In many illnesses and conditions, cytokine levels are cross-sectionally associated with depression risk. 19-21 This includes coronary disease, 22-26 cancer, 27-32 infectious illness, 33-36 multiple sclerosis, 37 dermatitis, 38, 39 lupus, 40, 41 kidney disease, 42, 43 chronic alcohol use, 44, 45 pregnancy, 46, 47 etc. Among each of these conditions, depressed patients tend to have higher levels of inflammatory cytokines.…”

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confidence: 99%

Inflammatory cytokine-associated depression

Lotrich

2015

Brain Research

151

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Inflammatory cytokines can sometimes trigger depression in humans, are often associated with depression, and can elicit some behaviors in animals that are homologous to major depression. Moreover, these cytokines can affect monoaminergic and glutamatergic systems, supporting an overlapping pathoetiology with major depression. This suggests that there could be a specific major depression subtype, inflammatory cytokine-associated depression (ICAD), which may require different therapeutic approaches. However, most people do not develop depression, even when exposed to sustained elevations in inflammatory cytokines. Thus several vulnerabilities and sources of resilience to inflammation-associated depression have been identified. These range from genetic differences in neurotrophic and serotonergic systems to sleep quality and omega-3 fatty acid levels. Replicating these sources of resilience as treatments could be one approach for preventing “ICAD”.

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Th1/Th2 cytokine profile in childhood-onset systemic lupus erythematosus

Cited by 49 publications

References 77 publications

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Inflammatory cytokine-associated depression

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