scholarly journals Aging as a Risk Factor on the Immunoexpression of Pro-Inflammatory IL-1β, IL-6 and TNF-α Cytokines in Chronic Apical Periodontitis Lesions

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 14
Author(s):  
Quésia Euclides Teixeira ◽  
Dennis de Carvalho Ferreira ◽  
Alexandre Marques Paes da Silva ◽  
Lucio Souza Gonçalves ◽  
Fabio Ramoa Pires ◽  
...  

Persistent inflammatory responses in the elderly may act as modifiers on the progression and repair of chronic apical periodontitis lesions (CAPLs). While the involvement of IL-1β, IL-6 and TNF-α in inflammatory responses and, particularly, in CAPL has been documented, their expression in elderly patients needs to be further characterized. Therefore, the purpose of this study was to evaluate and compare the expressions of pro-inflammatory cytokines in CAPL from elderly individuals with young/middle-aged individuals. Thirty CAPL (15 cysts and 15 granulomas) from elderly patients (>60 years) and 30 CAPL (15 cysts and 15 granuloma) from young/middle-aged individuals (20–56 years) were selected. Immunohistochemical reactions were performed against IL-1β, IL-6 and TNF-α. The slides were subdivided into five high-magnification fields and analyzed. The number of positive stains was evaluated for each antibody. There was no significant difference between the cytokines when the cysts and granuloma were compared in the two groups. In the young/middle-aged, only IL-1β showed a difference and was significantly higher in granulomas (p = 0.019). CAPL pro-inflammatory cytokine levels in the elderly were significantly higher than in young/middle-aged individuals (p < 0.05). The pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were significantly higher in CAPL in the elderly compared with the young/middle-aged group. Further elaborate research studies/analyses to elucidate the reasons for and consequences of inflammation in the elderly are recommended.

2021 ◽  
Author(s):  
Fanny Ponthieux ◽  
Nicolas Dauby ◽  
Evelyne Maillart ◽  
Jean-François Fils ◽  
Julie Smet ◽  
...  

Abstract Early evidence during the COVID-19 pandemic indicated high levels of IL-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic.We aimed to monitor IL-6 and several inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Fifteen critically ill SARS-CoV-2 PCR confirmed cases were enrolled and serum samples were collected during 8 days, before and following administration of a single dose of TCZ. In parallel, a control group consisting of 8 non-treated COVID-19 patients not receiving TCZ was established. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, TNF-α and INF-γ) and of IL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18 and IL-6R levels in the treated patients with maximal values reached 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. There was no significant difference in cytokine levels between survivors (TCZ/S) or non-survivors (TCZ/D). This observation suggests that some inflammatory pathways escape IL-6R blockade leading to an increase in several pro-inflammatory cytokines. Our findings could highlight an anti-inflammatory role of IL-6 and may explain why TCZ has failed to improve survival in critically ill COVID-19 patients when given alone.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.


2020 ◽  
pp. 088506662091298
Author(s):  
Suresh Kumar Angurana ◽  
Arun Bansal ◽  
Jayashree Muralidharan ◽  
Ritu Aggarwal ◽  
Sunit Singhi

Objective: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. Design: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. Setting: Pediatric intensive care unit of a tertiary level teaching hospital in India. Patients: Fifty children with severe sepsis aged 3 months to 12 years. Material and Methods: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor β1 [TGF-β1]) cytokines. Primary Outcome: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). Secondary Outcomes: To compare cytokine levels among survivors and nonsurvivors. Results: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-β1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = −0.257, P = .09) and TGF-β (ρ = −0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = .002, respectively. Conclusion: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.


2019 ◽  
Author(s):  
Alireza Ghanavatinejad ◽  
Nesa Rashidi ◽  
Mahroo Mirahmadian ◽  
Simin Rezania ◽  
Mahdokht Mosalaei ◽  
...  

Abstract Background: There is a significant association between intrauterine infection-associated inflammatory responses and such pregnancy complications as abortion and preterm labor. Here, we aimed to investigate anti-inflammatory effects of 1,25 (OH)2 D3 on pro-inflammatory cytokines secretion and expression of TLR2, TLR4 and MyD88 in endometrial stromal cells (ESCs) and whole endometrial cells (WECs). Method: WECs were treated with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) and ESCs were treated with LPS. IL-6, IL8 and TNF-α were quantified using ELISA technique. TLR2, TLR4 and MyD88 expression were assessed by RT-qPCR. TLR4 expression at the protein level was studied by Western blot technique. Results: 1,25 (OH)2 D3 significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pre-treatment increased production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pre-treatment markedly reduced LPS-induced TLR-4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pre-treated with 1,25 (OH)2 D3 before stimulation with LPS. Conclusion: 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintenance of endometrial immune homeostasis through controlling potentially harmful inflammatory responses associated with female reproductive tract infections. Key words: Vitamin D3, Endometrium, Inflammation, Toll like receptors, Pro-inflammatory cytokines


2019 ◽  
Vol 47 (5) ◽  
pp. 393-399
Author(s):  
A. A. Novikov ◽  
Е. N. Aleksandrova ◽  
G. V. Lukina

Background: An important characteristic of immune pathology in rheumatoid arthritis (RA) is a B-cell tolerance defect, associated with autoantibodies production, and antigen-specific activation of Th-1 CD4+ T lymphocytes with an excess production of pro-inflammatory cytokines compared to anti-inflammatory ones. Pro-inflammatory cytokines contribute to the development of local inflammatory effects, induce bone destruction and pannus formation, and contribute to the development of autoimmune abnormalities and systemic manifestations. Anti-inflammatory cytokines are able to reduce the rate of joint destruction. There is evidence of the involvement of Th2 cytokines in the development of early RA. These facts suggest the need for a thorough investigation into the balance between the Th1 and Th2 types of immune response at different stages of the disease.Aim: To assess the importance of сytokine profiling in the evaluation of immune abnormalities in RA.Materials and methods: In this descriptive, controlled, retrospective study, we examined 118 patients with RA and 33 healthy donors as a control group. Serum IgM rheumatoid factor (RF) and C-reactive protein (CRP) levels were measured by immunonephelometry; anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) were determined by an enzyme immunoassay, cytokines levels with "xMAP" technique.Results: Serum cytokine levels vary depending on RA duration. The cytokine profile in early RA, unlike that in established RA with a duration of more than 6 months, is characterized by higher levels of pro-inflammatory (MIP-1α), Th1 (IFN-γ), and Th17 (IL-17) cytokines, colony-stimulating factors (IL-7, G-CSF), and chemokines (IL-8, IP-10) (p < 0.05 for all parameters). In established RA, the levels of pro-inflammatory (IL-1β, -6, -15, TNF-α), anti-inflammatory (IL-1ra, IL-10, IL-13, IL-5), Th1 (IL-2, IL-12), Th2 (IL-9) cytokines and colony-stimulating factors (G-CSF, GM-CSF) correlate with the concentrations of IgM RF and antibodies to citrullinated proteins (antiCCP, anti-MCV) (all p < 0.05). There was also а correlation between CRP and pro-inflammatory (IL-1β, IL-6, TNF-α), Th1 (IL-12), Th2 (IL-5, IL-9) cytokine levels and between DAS28 and pro-inflammatory cytokine (IL-6) and colony-stimulating factor (G-CSF) levels (all p < 0.05). Conclusion: In RA, cytokines, chemokines and colony-stimulating factors mirror the inflammatory activity of the disease. Changes in blood concentrations of cytokines enable to get an insight into the complex interplay of numerous mediators of innate and acquired immunity


Author(s):  
О.А. Осипова ◽  
Н.И. Клюшников ◽  
Е.В. Гостева ◽  
О.Н. Белоусова ◽  
Н.И. Жернакова ◽  
...  

Цель исследования - изучение роли цитокинов, соотношения нейтрофилов и лимфоцитов в развитии постинсультной депрессии (ПД) у больных пожилого возраста. В исследование были включены 110 больных с острым ишемическим инсультом, из них 60 человек среднего возраста (52±5 лет) и 50 - пожилого возраста (66±4 года). Контрольную группу составили 20 человек среднего возраста без инсульта в анамнезе. Через 3 мес наблюдения ПД в пожилом возрасте развилась у 28 (56 %) больных, в среднем возрасте - у 26 (43,3 %). Больные пожилого возраста с ишемическим инсультом, у которых развилась ПД, были достоверно старше (7,9 %, р<0,05), чаще имели артериальную гипертензию (12,4 %, р<0,05), уровень гликемии выше на 16,1 % (р<0,05), триглицеридов - на 14 % (р<0,05), ЛПНП - на 12,8 % (р<0,05). Больные среднего возраста с ПД имели ИМТ выше на 8,1 % (р<0,05), уровень гликемии - на 9,6 % (р<0,05), триглицеридов - на 10,9 % (р<0,05), ЛПНП - на 9,7 % (р<0,05), чем больные без депрессии. Пожилые больные с ишемическим инсультом и ПД имели более высокий уровень цитокинов - IL-1β был выше на 35,4 % (р<0,01), TNF-α - на 27 % (р<0,01), INF-γ - на 18 % (р<0,01), чем у больных без ПД. У больных пожилого возраста с ПД соотношение нейтрофилов и лимфоцитов (Н/Л) было на 46 % (p<0,001) выше, чем у больных без ПД. В группе больных пожилого возраста при наличии ПД соотношение Н/Л было на 50 % (p<0,001) выше, чем в аналогичной группе среднего возраста. Таким образом, у пожилых больных с ишемическим инсультом уровень маркеров воспаления может иметь прогностическое значение в развитии постинсультной депрессии. The aim of the study was to study the role of cytokines, the ratio of neutrophils and lymphocytes in the development of post-stroke depression in elderly patients. The study included 110 patients with acute ischemic stroke, including 60 middle-aged people (52±5 years) and 50 elderly people (66±4 years). The control group consisted of 20 middle-aged people without a history of stroke. After 3 months of follow-up, post-stroke depression (PSD) developed in the elderly in 28 patients (56 %), in the middle age in 26 patients (43,3 %). Patients with ischemic stroke in the elderly who developed PSD were significantly older (7,9 %, p<0,05), more often had arterial hypertension (12,4 %, p<0,05), the level of glucose was 16,1 % higher (p<0,05), triglycerides by 14 % (p<0,05), LDL-C by 12,8 % (p<0,05). In middle age, patients with post-stroke depression had a body mass index higher by 8,1 % (p<0,05), a glucose level by 9,6 % (p<0,05), triglycerides by 10,9 % (p<0,05), LDL-C by 9,7 % (p<0,05) than patients without PSD. Elderly patients with ischemic stroke and PSD had higher levels of cytokines - IL-1β was 35,4 % higher (p<0,01), TNF-α by 27 % (p<0,01), INF-γ by 18 % (p<0,01) than in patients without PSD. In elderly patients with PSD, the ratio of neutrophils and lymphocytes (N/L) is 46 % (p<0,001) higher than in patients without PSD. In the elderly, in the presence of PSD, the N/L ratio was 50 % (p<0,001) higher than in the same middle-aged group. Thus, in elderly patients with ischemic stroke, the level of inflammatory markers may have a prognostic value in the development of post-stroke depression.


Cartilage ◽  
2019 ◽  
pp. 194760351988938
Author(s):  
Christoph Bauer ◽  
Christoph Stotter ◽  
Vivek Jeyakumar ◽  
Eugenia Niculescu-Morzsa ◽  
Bojana Simlinger ◽  
...  

Objective Cobalt and chromium (CoCr) ions from metal implants are released into the joint due to biotribocorrosion, inducing apoptosis and altering gene expression in various cell types. Here, we asked whether CoCr ions concentration-dependently changed viability, transcriptional activity, and inflammatory response in human articular chondrocytes. Design Human articular chondrocytes were exposed to Co (1.02-16.33 ppm) and Cr (0.42-6.66 ppm) ions and cell viability and early/late apoptosis (annexin V and 7-AAD) were assessed in 2-dimensional cell cultures using the XTT assay and flow cytometry, respectively. Changes in chondrocyte morphology were assessed using transmitted light microscopy. The effects of CoCr ions on transcriptional activity of chondrocytes were evaluated by quantitative polymerase chain reaction (qPCR). The inflammatory responses were determined by measuring the levels of released pro-inflammatory cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and tumor necrosis factor–α [TNF-α]). Results CoCr ions concentration-dependently reduced metabolic activity and induced early and late apoptosis after 24 hours in culture. After 72 hours, the majority of chondrocytes (>90%) were apoptotic at the highest concentrations of CoCr ions (16.33/6/66 ppm). SOX9 expression was concentration-dependently enhanced, whereas expression of COL2A1 linearly decreased after 24 hours. IL-8 release was enhanced proportionally to CoCr ions levels, whereas IL-1β, IL-6, and TNF-α levels were not affected by the treatments. Conclusions CoCr ions showed concentration- and time-dependent effects on articular chondrocytes. Fractions of apoptotic articular chondrocytes were proportional to CoCr ion concentrations. In addition, metabolic activity and expression of chondrocyte-specific genes were decreased by CoCr ions. Furthermore, exposure to CoCr ions caused a release of pro-inflammatory cytokines.


2021 ◽  
Vol 27 (4) ◽  
pp. 343-350
Author(s):  
Yanfen Yao ◽  
Hong Wang ◽  
Xueqin Xi ◽  
Wei Sun ◽  
Junke Ge ◽  
...  

miR-150 was found to target the 3′-untranslated regions of AKT3, and the AKT pathway was affected by SR protein kinase 1 (SRPK1). However, the expression and significance of miR-150, AKT3 and SRPK1 in acute lung injury (ALI) were not clear. Here, we found that the expression of miR-150 was significantly reduced, while the expression of AKT3 and SRPK1 were markedly increased in LPS-treated A549, THP-1 and RAW 264.7 cells. miR-150 significantly decreased levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, reduced the expression of AKT3, but had no impact on SRPK1 expression compared with the control group in LPS-treated A549, THP-1 and RAW 264.7 cells. AKT3 silencing only reduced the production of pro-inflammatory cytokines and showed no effect on miR-150 and SRPK1 expression. Finally, we observed that miR-150 mimics and/or silencing of SRPK1 decreased the expression of AKT3 mRNA. Besides, over-expression of miR-150 or silencing of SRPK1 also reduced the expression of AKT3 protein, which exhibited the lowest level in the miR-150 mimics plus si-SRPK1 group. However, si-SRPK1 had no effect on miR-150 level. In conclusion, miR-150 and SRPK1 separately and cooperatively participate into inflammatory responses in ALI through regulating AKT3 pathway. Increased miR-150 and silenced SRPK1 may be a novel potential factor for preventing and treating more inflammatory lung diseases.


2013 ◽  
Vol 4 (1) ◽  
pp. 20-23
Author(s):  
A. N Zakirova ◽  
N. E Zakirova

Objective: to evaluate the severity of immuno-inflammatory responses under stable stenocardia in patients with ischemic heart disease (IHD). Patients and intervention: the study included 83 patients suffering from IHD. Among them 30 cases were diagnosed as functional class (FC)-II stenocardia, 27 cases as FC-III stenocardia and 26 cases as FC-IV stenocardia. The control group included 25 healthy persons. For characterizing the immuno-inflammatory responses we examined the level of C-reactive protein (CRP), pro-inflammatory (IL-1b, IL-6, TNF-α) and anti-inflammatory (IL-4, IL-10) cytokines by the immunoenzymic procedure. Results: FC-II stenocardia showed normal levels of CRP and pro-inflammatory cytokines. FC-III stenocardia was associated with a moderate increase in markers of an inflammation. FC-IV stenocardia was characterized by maximum levels of CRP and pro-inflammatory cytokines. Conclusion. The intensity of immuno-inflammatory responses depends on more or less serious course of stenocardia in patients with IHD.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4577-4577 ◽  
Author(s):  
Sun-Young Kim ◽  
Jong-Sun Park ◽  
Nak-Gyun Jeong ◽  
Dae-Chul Jeong ◽  
Bin Cho ◽  
...  

Abstract Purpose: Fungal infections are one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B (ABV) and itraconazole (ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines (IL-4, IL-1Ra) by ABV and ITZA. Methods: From October 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-1β, TNF-α, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results: Empirical antifungal agents were given to 37 patients (ABV 20, ITZA 17), and 30 patients (ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-1β was increased in ABV treatment group and the ratio of IL-1Ra/IL-1β is markedly decreased in ABV treatment group while increased in ITZA group. Conclusions: ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.


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