scholarly journals Interplay between IL-17 family members and angiogenic cytokines in subjects with systemic sclerosis.

Author(s):  
Agata Liszewska ◽  
Ewa Robak ◽  
Anna Woźniacka ◽  
Jaroslaw Bogaczewicz ◽  
Bożena Dziankowska-Bartkowiak ◽  
...  

IntroductionSystemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease characterized by immune system activation, vasculopathy, and collagen accumulation. Despite progressive fibrosis of the vasculature, compensatory angiogenesis is impaired. The cause of the shift towards anti-angiogenesis observed in SSc is unknown. The IL-17 cytokine family participates in the pathogenesis of SSc and angiogenesis.Material and methodsOur study aimed to evaluate levels and find relationships between the levels of proangiogenic cytokines and cytokines from the IL-17 family in 42 SSc subjects and 20 healthy controls. VEGF, PlGF, HGF, TGFβ1, GM-CSF, IL-17A, IL-17B, IL-17E and IL-17F were quantified in the sera of all participants by ELISA sandwich kits.ResultsSignificantly higher mean concentrations of PlGF compared to controls - mean value (19.3 pg/ml in the SSc group vs. 11.4 pg/ml in the control group; p<0.001) and of HGF (1931 pg/ml in the SSc group vs. 1483 pg/ml in controls; p<0.05). Mean serum TGFβ1 level was also significantly lower in the SSc group (781 pg/ml) than controls (35991 pg/ml; p<0.001). Among the IL-17 family, significantly higher mean concentrations of IL-17B (67.0 pg/ml vs. 2.6 pg/ml in controls; p<0,001), IL-17E (8.0 pg/ml vs 0.64 pg/ml in controls; p<0.001) and IL-17F (0.42 pg/ml vs. 0.0 pg/ml in controls; p< 0.01) were detected. Serum concentrations of HGF and PlGF correlated with the concentrations of IL17A, IL-17B, and IL-17E.ConclusionsIn conclusion, our findings indicate that selected cytokines from the IL17 family participate in the pathogenesis of SSc and are responsible for the vascular abnormalities associated with this disorder.

2016 ◽  
Vol 28 (6) ◽  
pp. 357-361 ◽  
Author(s):  
Han-Joon Kim ◽  
Yong-Ku Kim

BackgroundImmune system activation is involved in the pathophysiology of panic disorder (PD). We investigated INF-γ+874 A/T, TNF-α-308 G/A, and IL-10-1082 G/A single nucleotide polymorphisms (SNPs) to determine their association with PD.MethodThis study enroled 135 PD patients and 135 healthy controls. INF-γ+874 A/T (rs2430561), TNF-α-308 G/A (rs1800629), and IL-10-1082 G/A (rs1800896) were genotyped.ResultsThere were no differences in genotypes or allele frequencies between the patient and control groups, regardless of accompanying agoraphobia. However, for female patients, the G allele frequency in IL-10 SNP was higher in the control group than in the patient group. Additionally, the female control group had a higher frequency of the A/G and G/G genotype in the IL-10 SNP than the female patient group.ConclusionWe suggest that the G allele in IL-10-1082 G/A might have a role in reducing the manifestations of PD in female patients. Further studies are needed to extend and confirm our findings.


Pteridines ◽  
2000 ◽  
Vol 11 (3) ◽  
pp. 94-99 ◽  
Author(s):  
Guna Laganovska ◽  
Agris Martinsons ◽  
Bronislavs Pitrans ◽  
Bernhard Widner ◽  
Dietmar Fuchs

Summary In 40 cataract patients and in 51 patients without pseudoexfoliation (PES) we determined serum concentrations of neopterin, kynurenine, and selenium and concentrations of neopterin in aqueous humour from the anterior chamber of the eye. In addition, selenium content in lenses was determined. Significantly increased kynurenine and neopterin concentrations in serum and neopterin concentrations in aqueous humour were observed in mature cataract patients with PES compared to those without. These patients also presented with the lowest content of selenium in serum and lens, compared with cataract patients without PES. Increased concentrations of neopterin in serum and aqueous humour of the anterior chamber of eyes suggest an increased degree of oxidative stress in patients with PES. Thus, the results support the role of oxidative stress in the development of PES in cataract patients. The decreased content of selenium may elicit immune system activation via an increased oxidative stress as it is indicated by the increased formation of kynurenine and neopterin.


Author(s):  
O El-Ahmady ◽  
M Mansour ◽  
H Zoeir ◽  
O Mansour

There is significant research in the role of interleukins in lung disease, as the cytokines are important mediators in the host response to mycobacterium tuberculosis infection. Plasma from patients with pulmonary tuberculosis (TB) and healthy controls were investigated for their content of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-6 (IL-6) and leukotriene B4 (LTB4). LTB4 and IL-6 were measured by enzyme immunoassay after lipid extraction in the case of LTB4 while GM-CSF was measured by enzyme amplified sensitive immunoassay. Significantly elevated concentrations of IL-6 were found in far-advanced lesions of pulmonary tuberculosis patients, P < 0·05. However, nonsignificant increases of IL-6 were obtained in moderate lesions and minimal lesions compared to normal healthy subjects. Marked elevations of LTB4 were found in TB patients, the highest values being shown in patients with far-advanced lesions followed by moderately advanced and minimal lesions in relation to the mean value for normal healthy controls, P < 0·001 for all groups. 93% of the tuberculosis patients showed a higher level of LTB4 above the upper limit of the control group. In contrast there was no significant increase of GM-CSF in any of the TB subgroups. These results suggest that LTB4 and the interleukins may play a role in the pathogenesis of mycobacterium tuberculosis infection.


2020 ◽  
Vol 21 (14) ◽  
pp. 4985 ◽  
Author(s):  
Antonello Giovannetti ◽  
Elisabetta Straface ◽  
Edoardo Rosato ◽  
Marco Casciaro ◽  
Giovanni Pioggia ◽  
...  

Systemic sclerosis (SSc) is a rare chronic autoimmune disease associated with significant morbidity and mortality. Two main subsets of SSc are recognized: (i) diffuse cutaneous SSc with rapidly progressive fibrosis of the skin, lungs, and other internal organs; and (ii) limited cutaneous SSc, which is dominated by vascular manifestations, with skin and organ fibrosis generally limited and slowly progressing. In spite of intense investigation, both etiology and pathogenesis of SSc are still unknown. Genetic and environmental factors, as well as abnormalities of immune functions, are strongly suggested for etiology, while microvascular abnormalities, immune system activation, and oxidative stress are suggested for the pathogenesis. Recently, it has been found that a multitude of mediators and cytokines are implicated in the fibrotic processes observed in SSc. Among these, a central role could be exerted by “alarmins”, endogenous and constitutively expressed proteins/peptides that function as an intercellular signal defense. This review describes, in a detailed manner, the role of alarmins in the pathogenesis of scleroderma.


Author(s):  
A. Riccio ◽  
M. De Caterina ◽  
D. Natale ◽  
E. Grimaldi ◽  
G. Pronesti ◽  
...  

In this report we investigate the behaviour of the serum levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in the course of Systemic Sclerosis (SS). This cytokine is produced mainly by T and NK cells, and its possible role in the pathogenesis of SS has not been previously described in the literature. Serum GM-CSF levels were assayed in 10 female patients, ageing from 35 to 70, affected by SS. These patients were not suffering from other disorders and were not being treated with steroids or immunosuppressive drug. A solid phase immunoenzymatic method was used to assess the serum levels of GM-CSF. Reference values were previously determined in a control group of 36 healthy women blood donors (19 premenopausal and 17 postmenopausal) (x̄=20.1 ±12.3 pg/ml). All the patients but one showed significantly increased serum levels of GM-CSF (x̄= 120.9 ±125.5 pg/ml). The highest levels were found in the two oldest patients, who also had the longest clinical history of SS, but a clear correlation with age, disease duration or clinical manifestations was not evident, even if the postmenopausal age group patients showed a higher mean value of GM-CSF (x̄= 148.0±144.1 pg/ml) than that found in the premenopausal age group (x̄= 57.7±1.4 pg/ml) (in contrast with the findings in the control group). The absence of other pathogenic conditions in our patients suggests that the increase in serum levels of GM-CSF might be linked to the fibroblast proliferation which is typical of SS. However, our results do not explain the role played by this factor in the fibroblastic proliferation process and an in vitro study is necessary to clarify this aspect.


2021 ◽  
Vol 13 ◽  
Author(s):  
Md. Mahiuddin Ahmed ◽  
Noah R. Johnson ◽  
Timothy D. Boyd ◽  
Christina Coughlan ◽  
Heidi J. Chial ◽  
...  

Innate immune system activation and inflammation are associated with and may contribute to clinical outcomes in people with Down syndrome (DS), neurodegenerative diseases such as Alzheimer’s disease (AD), and normal aging. In addition to serving as potential diagnostic biomarkers, innate immune system activation and inflammation may play a contributing or causal role in these conditions, leading to the hypothesis that effective therapies should seek to dampen their effects. However, recent intervention studies with the innate immune system activator granulocyte-macrophage colony-stimulating factor (GM-CSF) in animal models of DS, AD, and normal aging, and in an AD clinical trial suggest that activating the innate immune system and inflammation may instead be therapeutic. We consider evidence that DS, AD, and normal aging are accompanied by innate immune system activation and inflammation and discuss whether and when during the disease process it may be therapeutically beneficial to suppress or promote such activation.


1997 ◽  
Vol 78 (05) ◽  
pp. 1327-1331 ◽  
Author(s):  
Paul A Kyrle ◽  
Andreas Stümpflen ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
Kurt Herkner ◽  
...  

SummaryIncreased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment Fl+2 (Fl+2) was determined in the patient’s plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher Fl+2 levels than patients without H-HC (mean 0.52 ± 0.49 nmol/1, median 0.4, range 0.2-2.8, versus 0.36 ± 0.2 nmol/1, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3,6,9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher Fl+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either Fl+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated Fl+2 level(s) followed by recurrent VTE. No statistical significant difference in the Fl+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.


2018 ◽  
Vol 15 (1) ◽  
pp. 74-78
Author(s):  
Mohammadali Nazarinia ◽  
Asghar Zare ◽  
Mohammad javad Fallahi ◽  
Mesbah Shams

Background:Systemic sclerosis is a disorder of connective tissue with unknown cause, affecting the skin and internal organs, characterized by fibrotic changes.Objective:To determine the correlation between serum homocysteine level and interstitial lung involvement in systemic sclerosis. </P><P> Materials and Methods: In this case – control study, 59 patients who fulfilled the ACR/EULAR classification criteria for systemic sclerosis and were referred to Hafez Hospital of Shiraz, Iran, were included as the case group. Fifty nine healthy subjects were involved as the control group. Patients were divided into two groups based on interstitial lung involvement and two subtypes, diffuse and limited type. Serum homocysteine, vitamin B12, and folate levels compared between the controls, and cases groups.Results:Of 59 case and control group, 53 (%89.8) were female and the mean age did not differ in both groups (P=0.929). Thirty five (%59.3) patients had interstitial lung involvement and 38(%64.4) had diffuse cutaneous systemic sclerosis. The mean serum homocysteine level was 13.9±6.3 µmol/L in the case and 13.7±9.2 µmol/L in the control group (P=0.86). The mean serum homocysteine level did not differ between the patients with and without interstitial lung involvement (P=0.52). The patients with lung involvement was older than those without lung involvement (P=0.004). Lung disease was more common in diffuse type (P=0.014).Conclusion:In our study, serum homocysteine level did not differ between the patients and healthy subjects. Also, there was no correlation between serum homocysteine level and lung involvement, but lung involvement was more common in older patients and also diffuse subtype.


2020 ◽  
Vol 06 ◽  
Author(s):  
Ngan Nguyen Hoang ◽  
Thang Duong Minh ◽  
Tuan Anh Hoang ◽  
Son Le Ngoc Bich ◽  
Duong Nguyen Huu ◽  
...  

Objectives: Evaluate the effects of "XGTQ" in the treatment of cirrhosis induced by Carbon tetrachloride (CCL4) in combination with alcohol and high-fat diet on Wistar rats. Materials and methods: Cirrhosis on white rats was induced by subcutaneously injecting CC14 at an initial dose of 5,0ml/kg, followed by 1,2ml/kg once a week in 10 weeks. Then, fed with synthetic food, added 20% fat, and 0.05% cholesterol and iron oxalate. Rats were administered every day with plain water and 1 day with water mixed with 30% ethanol. The rats were randomly divided into 5 groups and given distilled water (group 1 and 2 or control group), silymarin (group 3 or reference group) or the "XGTQ" drug extract (group 4, 5) for 4 weeks. Collected blood for biochemical test and liver were dissected to evaluate weight, morphology and quantified 4-hydroxyproline to evaluate fibrosis and collagen accumulation. Results: In cirrhotic wistar rats, "XGTQ" drug at 19.6 g/kg/24h and 58.8 g/kg/24h showed the ability of reducing the activity of enzymes AST, ALT in the blood (p<0.01), increasing plasma albumin and decreasing prothrobin time (p<.05); improving physical condition, macroscopic and microscopic images of H&E-stained liver; decreasing the concentration of hydroxyproline in the liver and reducing the level of cirrhosis on the masson-stained templates. The effects of "XGTQ" increased with the dose, and was equivalent to silymarin at the dose of 70 mg/kg/24h. Conclusion: The extract of "XGTQ" drug is effective in treating cirrhosis in Wistar rats.


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