scholarly journals Parasitic helminth infections in humans modulate Trefoil Factor levels in a manner dependent on the species of parasite and age of the host

2021 ◽  
Vol 15 (10) ◽  
pp. e0009550
Author(s):  
Babatunde Adewale ◽  
Jonathan R. Heintz ◽  
Christopher F. Pastore ◽  
Heather L. Rossi ◽  
Li-Yin Hung ◽  
...  

Helminth infections, including hookworms and Schistosomes, can cause severe disability and death. Infection management and control would benefit from identification of biomarkers for early detection and prognosis. While animal models suggest that Trefoil Factor Family proteins (TFF2 and TFF3) and interleukin-33 (IL-33) -driven type 2 immune responses are critical mediators of tissue repair and worm clearance in the context of hookworm infection, very little is known about how they are modulated in the context of human helminth infection. We measured TFF2, TFF3, and IL-33 levels in serum from patients in Brazil infected with Hookworm and/or Schistosomes, and compared them to endemic and non-endemic controls. TFF2 was specifically elevated by Hookworm infection in females, not Schistosoma or co-infection. This elevation was correlated with age, but not worm burden. TFF3 was elevated by Schistosoma infection and found to be generally higher in females. IL-33 was not significantly altered by infection. To determine if this might apply more broadly to other species or regions, we measured TFFs and cytokine levels (IFNγ, TNFα, IL-33, IL-13, IL-1β, IL-17A, IL-22, and IL-10) in both the serum and urine of Nigerian school children infected with S. haematobium. We found that serum levels of TFF2 and 3 were reduced by infection, likely in an age dependent manner. In the serum, only IL-10 and IL-13 were significantly increased, while in urine IFN-γ, TNF-α, IL-13, IL-1β, IL-22, and IL-10 were significantly increased in by infection. Taken together, these data support a role for TFF proteins in human helminth infection.

2021 ◽  
Author(s):  
Babatunde Adewale ◽  
Christopher F. Pastore ◽  
Heather L. Rossi ◽  
Li-Yin Hung ◽  
Jeff Bethony ◽  
...  

Helminth infections, including hookworms and Schistosomes, can cause severe disability and death. Infection management and control would benefit from identification of biomarkers for early detection and prognosis. While animal models suggest that Trefoil Factor Family proteins (TFF2 and TFF3) and interleukin-33 (IL-33)-driven type 2 immune responses are critical mediators of tissue repair and worm clearance in the context of hookworm infection, very little is known about how they are modulated in the context of human helminth infection. We measured TFF2, TFF3, and IL-33 levels in serum from patients in Brazil infected with Hookworm and/or Schistosomes, and compared them to endemic and non-endemic controls. TFF2 was specifically elevated by Hookworm infection, not Schistosoma or co-infection. This elevation was more strongly correlated with age than with worm burden. To determine if this might apply more broadly to other species or regions, we measured TFFs and cytokine levels in both the serum and urine of Nigerian school children infected with S. haematobium. We found that serum levels of TFF2 and 3 were reduced by infection, but urine cytokine levels were increased (IL-1β, TNFα, IL-13, and IL-10). Finally, to determine if TFF2 and 3 might have immunosuppressive effects, we treated stimulated or unstimulated PMBCs with recombinant human TFF2 or TFF3 and measured proinflammatory cytokine levels. We found that rhTFF2, but not rhTFF3, was able to suppress TNF alpha and IFN gamma release from stimulated human PMBCs. Taken together, these data support a role for TFF proteins in human helminth infection.


2020 ◽  
Vol 19 (5) ◽  
pp. 1023-1029
Author(s):  
Yongbo Zhang ◽  
Zhuo Wu ◽  
Yihui Yang ◽  
Lu Ding

Purpose: To investigate the effect of trifluorobenzamidine (TBI) on a mouse model of ovalbumin (OVA)- induced allergic rhinitis. Methods: Allergic rhinitis was established in mice via sensitization on days 1, 5 and 14 through intraperitoneal injection of OVA (100 μg) in PBS. On day 15, the mice were subjected to intranasal exposure to OVA (1.5 mg dissolved in PBS). Prior to 10 days of intranasal exposure to OVA, the micewere treated with TBI at doses of 5, 10 and 20 μg/kg. Cytokine levels were determined using enzymelinked immunosorbent assay (ELISA) kits, while cyclooxygenase (COX)-2 and caspase-1 activity were assayed with western blotting. Results: Treatment with TBI significantly (p < 0.05) reduced OVA-mediated increases in nasal rub scores, and decreased serum levels of IgE, TNF-α, thymic stromal lymphopoietin (TSLP), IL-1β and histamine in mice. It also significantly regulated spleen weight and IL-4 secretion (p < 0.05) in OVAadministered mice. TBI significantly downregulated the expressions of IL-5, IL-13, TNFα, TSLP, IL-1β and IL-6 (p < 0.05). Administration of TBI caused a marked reduction in OVA-mediated increase in caspase-1 activity in mice intranasal tissues, and also significantly reduced OVA-induced excessive production of MIP-2 and ICAM-1 (p < 0.05). Moreover, TBI prevented OVA-induced infiltration of eosinophils and mast cells into intranasal tissues (p < 0.05). Conclusion: TBI reduces levels of IgE and various pro-inflammatory cytokines in OVA-administered mice. It also regulates Th1:Th2 ratio, inhibited activity of caspase-1, suppressed mast cell/eosinophil infiltration and reduced ICAM-1 and MIP-2 levels. Therefore, TBI possesses inhibitory potential against rhinitis allergy, and thus can potentially be developed as a new treatment strategy for asthma. Keywords: Trifluorobenzamidine, Anti-inflammation, Allergic rhinitis, Cytokines, Caspase-1, Itching


2020 ◽  
Author(s):  
Lida Zare ◽  
Akram Eidi ◽  
Mohammad Safarian ◽  
Mohammad Kazemi Arababadi

Abstract Background Angiography is a safe cardiovascular technique for the diagnosis and treatment of the cardiovascular disorders. The potential effects of angiography on the cytokines are yet to be clarified completely. Interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) are the important pro-inflammatory cytokines that participate in the pathogenesis of artery stenosis. The aim of his project was to study the angiography effects on the serum levels of IL-8 and TNF-α. Methods Fifty-five participants in three groups, without, with one and with more than one artery stenosis, were explored in this project. Serum levels of IL-8 and TNF-α were measured in the participants before and after angiography using enzyme linked immunosorbent assay (ELISA) technique. Results Serum levels of IL-8, but not TNF-α, were significantly decreased following angiography. X-ray doses had moderate positive correlation with serum levels of TNF-α in the patients with more than one artery stenosis. Serum levels of IL-8 and TNF-α were not different among male and female participants in all groups. Discussion Angiography may be a protective factor for inflammation in IL-8 dependent manner. Using angiography in the patients with more than one artery stenosis needs to be executed cautiously.


2014 ◽  
Vol 42 (04) ◽  
pp. 905-919 ◽  
Author(s):  
Jian Zhong ◽  
Taotao Ma ◽  
Cheng Huang ◽  
Huanzhong Liu ◽  
Zhaolin Chen ◽  
...  

Macrophages play a crucial role in rheumatoid arthritis (RA). Their activation is the initial step of RA. This study was designed to detect the effects of total flavonoids from Litsea coreana Levl. (TFLC) on the complete Freund's adjuvant-induced (CFA-induced) arthritis (AA) in rats and to explore whether inflammatory cytokines were induced by the IRE1/mTORC1/TNF-α-dependant mechanism in peritoneal macrophages. In vivo, our data indicated that TFLC (100, 200 mg/kg, i.g. × 10 days) could significantly suppress secondary paw swelling and serum levels of TNF-α and IL-1β. Histopathological figures showed that TFLC treatment improved the morphologic changes of articular cartilages and synovium. Results of RT-PCR and western blotting demonstrated that TFLC suppressed expression of 78-KD glucose regulated protein (GRP78), X-box binding protein 1 (XBP1), mTOR complex 1 (mTORC1) and TNF-α in peritoneal macrophages of AA rats. Collectively, these results indicate that TFLC is able to ameliorate adjuvant-induced arthritis in a dose-dependent manner by suppressing the IRE1/mTORC1/TNF-α-regulated inflammatory response initiated in peritoneal macrophages.


2011 ◽  
Vol 89 (9) ◽  
pp. 665-673 ◽  
Author(s):  
Rui Zhao ◽  
Zhibao Chen ◽  
Guiyan Jia ◽  
Jian Li ◽  
Yaping Cai ◽  
...  

Diosmetin (DGVL) extracted from the traditional Chinese herb Galium verum L. has been found to have anticancer activity. In this study, the effects of DGVL on the thymus of U14-bearing mice were investigated. Using flow cytometry, peripheral blood lymphocytes were characterized based on the expression of surface markers for T helper cells (CD4+) and T suppressor cells (CD8+). Serum levels of tumor necrosis factor α (TNF-α), interleukin-2 (IL-2), IL-10, and transforming growth factor β1 (TGF-β1) and a cell proliferation assay were determined with an enzyme-linked immunosorbent assay. The expression of Fas and Fas ligand (FasL) on the thymus was determined by Western blotting. Our results showed that DGVL inhibited tumor growth and significantly increased the thymus weight compared with the control. Also, DGVL elevated serum levels of IL-2 and significantly reduced levels of TNF-α, TGF-β1, and IL-10 in a dose-dependent manner. Histological study and terminal dUTP nick end labeling staining results showed that DGVL protected thymus tissue against the onslaught of tumor growth by inhibiting thymus lymphocyte apoptosis. The cell proliferation assay revealed that DGVL might promote more thymus lymphocytes towards proliferation. Furthermore, the ratio of CD4+/CD8+ T lymphocytes was significantly increased from 0.69 to 2.29 by treatment with DGVL. Immunoblotting analyses revealed that the expression of Fas and FasL on the thymus was lower in mice in the DGVL treatment group than in the control mice. In conclusion, DGVL can inhibit tumor growth and protect tumor-induced apoptosis of the thymus, and the mechanism is closely associated with reduced cell death in the thymus and a Fas–FasL-dependent pathway.


2021 ◽  
Author(s):  
Chul-Hyun Cho ◽  
Du Hwan Kim ◽  
Eun Hee Baek ◽  
Du-Han Kim

Abstract Background The purpose of this study was to determine serum levels of sleep-related cytokines in patients with rotator cuff tear (RCT) and to investigate the correlations between serum levels of sleep-related cytokines and clinical scores. Methods Peripheral blood samples were collected from 63 study participants were divided into three groups: RCT patients with sleep disturbance (sleep disturbance group; SD group) (n = 21), RCT patients without sleep disturbance (normal sleep group; NS group) (n = 21), and patients with shoulder instability (control group) (n = 21). Serum concentration levels of sleep-related cytokines including interleukin-1α (IL-1α), IL-1β, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were measured via enzyme-linked immunosorbent assay. The associations between serum levels of sleep-related cytokines and clinical scores including the Visual Analogue Scale (VAS) pain score, the University of California at Los Angeles (UCLA) score, and the Pittsburgh Sleep Quality Index (PSQI) were analyzed. Results Serum concentration levels of TNF-α were significantly higher in the SD group compared with those of the NS and control groups (P = < 0.001 and 0.05). Serum levels of IL-8 and IL-10 were significantly higher in the SD group compared with those of control group (P = 0.01 and = 0.05), but did not differ significantly from that of the NS group (P > 0.05). Serum level of IL-6 was significantly lower in the SD group compared with those of the NS and control groups (P = < 0.001 and 0.01). There were no associations between serum levels of sleep-related cytokines and all clinical scores including VAS pain, UCLA, and PSQI scores (all P > 0.05). Conclusion The current findings suggest that TNF-α may play a significant role in the pathophysiology of sleep disturbance in patients with RCT and be a possible therapeutic target to improve sleep disturbance in patients with RCT.


1996 ◽  
Vol 24 (4) ◽  
pp. 430-434 ◽  
Author(s):  
J. M. J. Hammond ◽  
P. D. Potgieter

The cytokine cascade which is triggered by severe sepsis may contribute to progressive organ dysfunction and death from sepsis. This cascade may be accentuated by surgery for sepsis and pre-treatment with cytokine blockers could possibly ameliorate the response. This prospective controlled study determined the effect of surgery in 11 haemodynamically stable patients undergoing laparotomy for intra-abdominal sepsis. Serum levels of endotoxin, IL-1, IL-6, IL-8 and TNF-α were determined; blood cultures, features of systemic inflammatory response, and organ dysfunction were monitored over the perioperative period. There was considerable variation in the serum cytokine levels. The preoperative IL-6 levels were significantly elevated in the septic patients and a threefold increase in IL-6 levels occurred in both groups postoperatively. An increase in TNF-α did not achieve significance because of high levels in control patients with cancer. Cytokine release which occurs during abdominal surgery is increased in patients with intra-abdominal sepsis.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Diego Oliveira Miranda ◽  
Taís Aparecida Soares de Lima ◽  
Lucas Ribeiro Azevedo ◽  
Omar Feres ◽  
José Joaquim Ribeiro da Rocha ◽  
...  

The objective of this study was to investigate whether serum cytokine levels correlate with depression and anxiety in colorectal cancer (CRC) patients. Twenty patients hospitalized for surgical resection of CRC were included in the study group and twenty healthy volunteers comprised the control group. Depression and anxiety were analyzed using the Hospital Anxiety and Depression Scale (HADS), and serum levels of IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α, and TGF-βwere measured by Cytometric Bead Array. We found that more than half of CRC patients presented clinically significant levels of anxiety or depression, and 65% of them manifested a combination of severe anxiety and depression. CRC patients had increased serum levels of IL-1β, IL-6, IL-8, and TNF-α but lower IL-10 concentrations. Correlation analysis between HADS score and cytokine levels revealed a positive association of anxiety and/or depression with IL-1β, IL-6, IL-8, and TNF-α and a negative correlation with IL-10. These results indicate that circulating proinflammatory cytokines are involved in the pathophysiology of anxiety and depression in CRC patients. A better understanding of the molecular mechanisms involved in these psychological disorders will allow the design of therapeutic interventions that lead to an improved quality of life and overall survival of CRC patients.


Cephalalgia ◽  
2015 ◽  
Vol 35 (13) ◽  
pp. 1153-1161 ◽  
Author(s):  
Güneş Altıokka-Uzun ◽  
Erdem Tüzün ◽  
Esme Ekizoğlu ◽  
Canan Ulusoy ◽  
Sibel Yentür ◽  
...  

Objectives The pathogenesis of idiopathic intracranial hypertension (IIH) is currently unknown and there are speculations about the contribution of some immunologic factors. The aim of this study is to investigate the presence of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) and/or serum cytokine levels in patients with IIH. Methods Patients fulfilling revised diagnostic criteria for IIH were included. Their demographic, clinical, ophthalmologic and laboratory features were examined. Serum and CSF samples were detected by isoelectric focusing and immunoblotting for OCBs. The samples of IIH patients and control groups were investigated by ELISA for cytokine levels. Results We detected OCBs in eight (30.77%) patients diagnosed with IIH. There were no other obvious clinical and laboratory differences of IIH profiles between the patients with and without OCBs, but frequency of vision loss was significantly higher in the group with OCBs in comparison to OCB negatives ( p = 0.038). Patients with IIH had highly elevated TNF-α, IFN-γ, IL-4, IL-10, IL-12, IL-17 in their sera compared to patients with multiple sclerosis (MS) and healthy controls. Furthermore, all cytokines except TNF-α in the CSF were found significantly higher in IIH patients compared to MS controls. Conclusion The presence of OCBs and elevated cytokine levels in IIH patients may support an immunologic background in the pathophysiological pathway of this disorder.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Xinlu Yuan ◽  
Binbin Dai ◽  
Liyan Yang ◽  
Beiduo Lin ◽  
Enqin Lin ◽  
...  

Abstract The purpose of the present study was to explore the effects of emodin on renal injury in a BXSB mouse model of lupus and its mechanisms. BXSB mice were fed different concentrations of emodin (0, 5, 10 and 20 mg/kg.d), and the levels of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α) and fibronectin (FN) levels in the glomeruli and serum levels of the anti-dsDNA antibody were determined. Mesangial cells (MCs) were cultured in vitro, and IgG-type anti-dsDNA antibody and/or emodin were added to the MC culture supernatant. In addition, TNF-α small interfering RNA (siRNA) was transfected into MCs to explore the mechanism of action of emodin. The results showed that the mice fed emodin presented decreases in the urinary protein content and glomerular TNF-α, ICAM-1 and FN levels (P&lt;0.05). Moreover, the urine protein, TNF-α, ICAM-1 and FN levels were decreased in a dose-dependent manner (P&lt;0.05). In vitro, the anti-dsDNA antibody group exhibited increased levels of ICAM-1 and TNF-α (P&lt;0.05), and the anti-dsDNA antibody group showed myofibroblast-like structural changes. The aforementioned indexes were decreased in the emodin group (P&lt;0.05), and the extent of transdifferentiation was significantly reduced. Moreover, the level of ICAM-1 decreased with the down-regulation of TNF-α (P&lt;0.05). Emodin reduced the urine protein levels and serum levels of the anti-dsDNA antibody in a mouse model of lupus nephritis (LN). The underlying mechanism may be related to decreased levels of TNF-α, ICAM-1 and FN and the inhibition of dsDNA antibody-induced MC damage.


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