scholarly journals Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Vinod Umare ◽  
Vandana Pradhan ◽  
Milind Nadkar ◽  
Anjali Rajadhyaksha ◽  
Manisha Patwardhan ◽  
...  

Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1βwere found to be significantly higher in SLE patients than healthy controls (P<0.001). Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL) was significantly higher (P=0.0430) than those of inactive disease patients (43.85±63.36 pg/mL). Mean level of TNF-αwas44.76±68.32 pg/mL for patients with active disease while it was25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161). Similar results were obtained for IL-1β(P=0.0002). Correlation between IL-6, TNF-α, and IL-1βserum levels and SLEDAI score was observed (r=0.20,r=0.27, andr=0.38, resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.

Lupus ◽  
2017 ◽  
Vol 26 (9) ◽  
pp. 975-982 ◽  
Author(s):  
M Sahebari ◽  
G Roshandel ◽  
N Saadati ◽  
M Saghafi ◽  
N Abdolahi ◽  
...  

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 ( P = 0.01, standardized beta –0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis.


2010 ◽  
Vol 37 (10) ◽  
pp. 2046-2052 ◽  
Author(s):  
MO YIN MOK ◽  
HAI JING WU ◽  
YI LO ◽  
CHAK SING LAU

Objective.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.Methods.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.Results.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.Conclusion.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.


Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2076-2085 ◽  
Author(s):  
Q Wu ◽  
Q Yang ◽  
H Sun

Objective The objective of this article is to investigate whether the aberrant expression of collagen triple helix repeat containing-1 (CTHRC1) from patients with systemic lupus erythematosus (SLE) could contribute to the pathogenesis of lupus. Methods We divided SLE patients into active groups (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥ 6) and inactive groups (SLEDAI score < 6). Serum concentrations of CTHRC1, interferon alpha, interleukin (IL)-28A and IL-28B were determined using an enzyme-linked immunosorbent assay in a group of 40 patients with SLE. Results were compared with those from 23 healthy controls. Results Serum CTHRC1 protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease displayed higher CTHRC1 levels compared with those with inactive disease as well. There was a positive association between serum CTHRC1 levels and SLEDAI and erythrocyte sedimentation rate, and a negative correlation with complement 3 and 4. Moreover, serum CTHRC1 levels were higher in SLE patients with arthritis and anemia compared with patients without the above-mentioned manifestations. Conclusions These findings indicate CTHRC1 probably plays an important part in the pathogenesis of SLE, and is positively associated with disease activity, while it also likely refers to the development of arthritis and anemia in SLE. Therefore, CTHRC1 may provide a novel research target and shed new light on the pathogenesis and therapy of SLE.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Lei Gu ◽  
Lingxiao Xu ◽  
Xiaojun Zhang ◽  
Wenfeng Tan ◽  
Hong Wang ◽  
...  

The aim of this paper is to investigate the correlation of glucocorticoid-induced tumor necrosis factor receptor- (TNFR-) related protein ligand (GITRL) with disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Serum GITRL levels were measured in 58 patients with SLE and 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of serum GITRL levels with SLEDAI, laboratory values, and clinical manifestations were assessed. Serum GITRL levels were determined by ELISA. Serum GITRL levels were markedly increased in patients with SLE compared with healthy controls (mean 401.3 ng/mL and 36.59 ng/mL, resp.;P<0.0001). SLE patients with active disease showed higher serum GITRL levels compared to those with inactive disease (mean 403.3 ng/mL and 136.3 ng/mL, resp;P=0.0043) as well as normal controls (36.59 ng/mL;P<0.0001). Serum GITRL levels were positively correlated with SLEDAI, titers of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and IgM and negatively correlated with complement3 (C3). Serum GITRL levels were higher in SLE patients with renal involvement and vasculitis compared with patients without the above-mentioned manifestations.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Ling Zhou ◽  
Guoyuan Lu ◽  
Lei Shen ◽  
Linfeng Wang ◽  
Mingjun Wang

Our research investigates the serum levels of three angiogenic factors in the AF family, namely, placenta growth factor (PlGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), in 54 patients with SLE (SLE group) and 28 healthy controls (normal control) through ELISA measurement. And their interrelationships were also systematically analyzed. The SLE patients were then divided into active SLE group and inactive SLE group according to the SLEDAI score. The results show that serum levels of PlGF, bFGF, and VEGF in all SLE group and active SLE group were higher than those in normal controls. Serum levels of PlGF and bFGF in inactive SLE group were higher than those in normal controls. The level of PlGF was positively correlated with VEGF in SLE patients and positive correlation is also shown in bFGF with VEGF. The levels of PlGF and VEGF in SLE patients were positively correlated with both ESR and SLEDAI score. Thus a tentative conclusion can be drawn that the serum levels of the angiogenic factors, for example, PlGF, bFGF, and VEGF, may be relevant in the pathogenesis of SLE, and the concentrations of PlGF and VEGF seem to be the markers of SLE activity.


2011 ◽  
Vol 38 (5) ◽  
pp. 877-884 ◽  
Author(s):  
MINORU HASEGAWA ◽  
MANABU FUJIMOTO ◽  
YASUHITO HAMAGUCHI ◽  
TAKASHI MATSUSHITA ◽  
KATSUMI INOUE ◽  
...  

Objective.To clarify the clinical significance of concentrations of serum Clara cell 16-kDa protein (CC16; previously denoted CC10) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc); and to compare CC16 levels with levels of the current most reliable serum markers for PF, such as Krebs von den Lungen-6 (KL-6) antigen and surfactant protein-D (SP-D).Methods.Serum levels of CC16, KL-6, and SP-D were determined by ELISA in 92 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. In a retrospective longitudinal study, correlation of serum CC16 levels with the activity of PF was assessed in 16 SSc patients with PF.Results.Although CC16 levels were higher in patients with SSc than in SLE patients or healthy controls, the difference was not significant. Increased serum CC16 levels were associated with involvement of PF, especially active PF, as well as KL-6 and SP-D. Receiver operating characteristic curve analysis revealed that the utility of CC16 is slightly inferior to KL-6, but was comparable with that of SP-D for detecting PF in patients with SSc. In the longitudinal study, serum levels of CC16, KL-6, and SP-D were significantly decreased in the inactive disease phase compared to the active disease phase.Conclusion.CC16 levels can be used as a potential serum biomarker for PF in addition to KL-6 and SP-D in patients with SSc.


2021 ◽  
Vol 12 ◽  
Author(s):  
Benoit Brilland ◽  
Maxime Bach-Bunner ◽  
Christopher Nunes Gomes ◽  
Vincent Larochette ◽  
Etienne Foucher ◽  
...  

ObjectiveInterleukin-26 (IL-26) has a unique ability to activate innate immune cells due to its binding to circulating double-stranded DNA. High levels of IL-26 have been reported in patients with chronic inflammation. We aimed to investigate IL-26 levels in patients with systemic lupus erythematosus (SLE).MethodsIL-26 serum levels were quantified by ELISA for 47 healthy controls and 109 SLE patients previously enrolled in the PLUS study. Performance of IL-26 levels and classical markers (autoantibodies or complement consumption) to identify an active SLE disease (SLE disease activity index (SLEDAI) score &gt; 4) were compared.ResultsIL-26 levels were significantly higher in SLE patients than in controls (4.04 ± 11.66 and 0.74 ± 2.02 ng/mL; p = 0.005). IL-26 levels were also significantly higher in patients with active disease than those with inactive disease (33.08 ± 21.06 vs 1.10 ± 3.80 ng/mL, p &lt; 0.0001). IL-26 levels correlated with SLEDAI score and the urine protein to creatinine ratio (uPCR) (p &lt; 0.001). Patients with high IL-26 levels had higher SLEDAI score, anti-DNA antibodies levels, and uPCR (p &lt; 0.05). They presented more frequently with C3 or C4 complement consumption. Lastly, IL-26 showed stronger performance than classical markers (complement consumption or autoantibodies) for active disease identification.ConclusionsOur results suggest that, in addition to classical SLE serological markers, the measurement of IL-26 levels may be a useful biomarker for active disease identification in SLE patients.


2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Ewa Robak ◽  
Agnieszka Wierzbowska ◽  
Magdalena Chmiela ◽  
Liliana Kulczycka ◽  
Anna Sysa-Jędrejowska ◽  
...  

We investigated the serum concentration of total metalloproteinase-9 (tMPP-9), active MMP-9 (aMMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in a group of 41 patients with SLE and 20 healthy controls. Serum levels of tMMP-9 and TIMP-1 were assessed by an enzyme-linked immunosorbent assay (ELISA) and aMMP-9 by fluorometric assay. The tMMP-9 level was lower in SLE patients (mean 262 ng/mL) than in healthy volunteers (mean 325 ng/mL) (P=.048). Similarly, aMMP-9 level was lower in SLE patients (mean 121 ng/mL) than in control group (mean 169 ng/mL) (P=.0355) and lower in active SLE (mean 54 ng/mL) than in inactive disease (mean 99 ng/mL) (P=.033). TIMP-1 level was also lower in SLE patients (mean 181 ng/mL) than in control group (mean 233 ng/mL) (P=.004). In SLE patients, a positive correlation was found between tMMP-9 and aMMP-9 (ρ=0.568;P=.001). We also found a positive correlation of tMMP-9 and TIMP-1 with VEGF concentrations (ρ=0.450,P=.005andρ=0.387;P=.018, resp). tMMP-9, aMMP-9, and TIMP-1 serum levels are lower in SLE patients than in healthy control group.


Lupus ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 748-754 ◽  
Author(s):  
R C Li ◽  
J Guo ◽  
L C Su ◽  
A F Huang

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 47.2-47
Author(s):  
C. Gioia ◽  
B. Lucchino ◽  
C. Iannuccelli ◽  
G. Dolcini ◽  
M. DI Franco

Background:Fibromyalgia (FM) is a common rheumatic disease characterized by chronic widespread pain, sleep and mood disorders. A higher prevalence of FM in women compared with men is well known, although the specific differences in clinical manifestations related to gender are still poorly defined. Brain-Derived Neurotrophic Factor (BDNF) is an endogenous growth factor that gained attention for its potential as biomarker of several diseases, including FM and depression.Objectives:The aims of this study were to investigate gender-related difference among males and females affected by FM in clinical manifestations, depressive features and BDNF serum level, evaluating also the diagnostic potential of the latter.Methods:We consecutively enrolled adult patients affected by FM (ACR 2016) referring to our out-patient clinic. Each subject underwent clinical and answered to questionnaires for the severity of FM symptoms (Revised Fibromyalgia Impact Questionnaire, R-FIQ) and depressive symptoms (Beck Depression Inventory-II, BDI-II). We collected blood samples from a subgroup of patients of both sexes, matched for age, for BDNF serum level dosage through ELISA. BDNF levels were assessed also in a control group, matched for sex and age.Results:The cohort was composed by 201 FM patients (172 F, 29 M), mean age 49.13. Females showed higher values of R-FIQ total score (p=0,0005) as well the specific items of the R-FIQ for pain (p=0,013), fatigue (p=0,014), memory problems (p=0,007), tenderness to touch (p<0,0001), balance problems (p<0,0001) and sensitivity to environmental stimuli (p=0,012) when compared with males (fig. 1). There was no difference in BDI-II between males and females, but notably male patients reported a significantly higher frequency of coexisting depressive disorder (p=0,038) (fig. 2). Serum BDNF levels were evaluated in 40 FM patients and 40 healthy controls (HC) (F:M 1:1). BDNF levels were significantly lower in FM patients compared with HC (p<0,0001). Among FM patients, BDNF levels were lower in males compared with females (p<0,0001) (fig.3). BDNF did not correlate with any clinical and clinimetric parameter. BDNF showed a good diagnostic performance (AUC=0,89, CI95%=0,82-0,9630, p<0,0001) (fig. 4). At a cut-off value <6,47 ng/dl, BDNF showed a specificity of 75% and a sensibility of 92,31%,(CI 95%=79,68-97.35) for FM identification (LR=3,692).Conclusion:FM clinical manifestations are strongly dependant from gender. While females present a more severe disease and a higher burden of symptoms, mood disorders tend to be a major characteristic of males with FM. Reduced BDNF serum levels have been reported as typical of depressive disorders. Our findings of lower BDNF levels in male FM patients compared to females support this hypothesis. BDNF have potential as biomarker of the disease and should be validated in larger cohorts.References:[1]Sarzi-Puttini et al. Nature Reviews 2020[2]Colucci-D’Amato et al. Int J Molecular Sciences 2020[3]Nugraha et al. Rheumatol Int 2012[4]Schmitt et al. Ann Med 2016[5]Melchior et al. Neuroscience 2016[6]Stefani et al. Neuroscience Letters 2012Disclosure of Interests:None declared


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