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1.
Gene ; 722: 144098, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494241

RESUMO

This study evaluated the possible association between SNPs in cytokines coding genes, namely IL10, IL6 and IFNG, cytokines serum levels and clinical assessment' scores in patients with Rheumatoid Arthritis(RA). SNPs genotyping was performed in 126 RA patients and 177 healthy individuals with Taqman probes specific for IL10 -1082 (T>C, rs1800896);INFG -1616 (A>G, rs2069705) and IL6 -174 (G>C, rs1800795) variants,positioned in regulatory regions. Cytokine Bead Array (CBA) was used to measure cytokine levels. We found association between INFG -1616 G allele(p = 0.0210; OR = 1.605) and INFG -1616 GG genotype (p = 0.0268; OR =2.609) and RA susceptibility. We also observed association between IL10 -1082 TT genotype and high clinical disease activity index (CDAI) values (p = 0.026; OR = 1.906; 95% CI = 1.082 - 3.359), IL10 -1082 CC genotype and low CDAI values (p = 0.016; OR = 0.256) and INFG -1616 AA and high CDAI values (p = 0.025; OR = 2.919). IL10 -1082 CC also exhibited the lowest IL-10 levels than IL10 -1082 TT (p = 0.020) and IL10 -1082 TC (p = 0.032). Finally, we verified higher IL-6 value in the RA patients than healthy control group (p = 0.007) and an association between high IL-6 levels and increased CDAI (r = 0.4648, p = 0.0015); DAS 28 (r = 0.3933, p= 0.0091), presence of bone erosions (r = 0.3170, p = 0.0361), ESR levels(r = 0.3041, p = 0.0448) and IFN-γ levels (r = 0.3049, p = 0.0468).Altogether, we suggest that IL10 -1082 (T>C, rs1800896) and INFG -1616(A>G, rs2069705) polymorphisms as well as IL-6 levels alterations may play a role for prognostic and disease follow-up.


Assuntos
Artrite Reumatoide/genética , Interferon gama/genética , Interleucina-10/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade
2.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2637-2643, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359734

RESUMO

To investigate the effect of Fuyanshu Capsules combined with Western medicine antibiotics on symptoms and inflammatory factors IL-10 and IL-1ß in patients with pelvic inflammatory disease and its possible mechanism. Totally 112 patients with pelvic inflammatory disease of damp-heat stagnation treated since April 2017 to April 2018 were randomly divided into treatment group( group A,57 cases) and control group( group B,55 cases). The treatment group was given Fuyanshu Capsules for 56 d,and levofloxacin hydrochloride tablets and metronidazole tablets for 14 d. The control group was given Fuyanshu Capsules as its analogue. The curative rate,effective rate and inefficiency,serum IL-10 and IL-1ß levels were compared between the two groups. The curative effect was evaluated with McCormack score and traditional Chinese medicine( TCM) syndrome score. The recurrence rate and chronic pelvic pain were followed up after one menstrual cycle. It was found that the curative rate and effective rate of group A were higher than those of group B after treatment. After 28 d of treatment,there was a difference in the effective rate of TCM syndrome score between group A and group B( 62. 71% vs 8. 47%,P < 0. 01). After 56 d of treatment,serum IL-10 increased,while IL-1ß decreased in group A,which was significantly different from that in group B( P<0. 01). The recurrence rate of PID and chronic pelvic pain in group A were significantly lower than those in group B( P<0. 01). The results showed that Fuyanshu Capsules combined with levofloxacin and metronidazole could alleviate the clinical symptoms and signs of chronic pelvic inflammation of damp-heat stagnation type,reduce the recurrence rate of pelvic inflammation,relieve pelvic pain,and alleviate the inflammation status of patients by regulating the expression of IL-10 and IL-1ß in peripheral serum.


Assuntos
Antibacterianos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Inflamatória Pélvica/tratamento farmacológico , Cápsulas , Feminino , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Levofloxacino , Medicina Tradicional Chinesa , Metronidazol
3.
Egypt J Immunol ; 26(1): 69-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332997

RESUMO

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Tumors can recruit and promote the expansion of regulatory T cells (Tregs) to suppress antitumor immune responses for survival and progression. Furthermore, there is a strong evidence for the potential roles of cytokines in promoting HCC carcinogenesis and progression. We aimed to evaluate the frequency of Treg cells and serum levels of IL6 and IL10 before and after transarterial chemoembolization (TACE). We carried out a cross-sectional study at Assiut University hospitals that included 34 HCC patients and 10 matched apparently healthy controls. Peripheral Treg frequency was evaluated by Flow cytometry. IL6 and IL10 serum levels were evaluated by ELISA before and after TACE. HCC patients had a significantly higher level of IL6 and IL10 when compared to the control group (P=0.0002, P < 0.0001), respectively. However, after treatment, there was an elevation in the levels of IL6 and IL10 followed by a decrease to the baseline levels. Patients with large tumors (≥5 cm) showed higher levels of both IL 6 and IL 10 than those with smaller tumors. Moreover, HCC patients showed a higher frequency of Treg cells in comparison to the controls (P=0.002). No significant correlation was observed between the frequency of Treg cells and IL10 before and after treatment (r=0.38, P=0.30). In conclusion, HCC patients have significantly higher levels of IL 6, IL 10 and a higher percentage of Tregs than control individuals. Treg levels are altered after chemoembolization. IL 6 have a potential in reflecting the patient's condition after treatment, thus, can help in monitoring therapy.


Assuntos
Carcinoma Hepatocelular/imunologia , Quimioembolização Terapêutica , Hepatite C/imunologia , Interleucina-10/sangue , Interleucina-6/sangue , Neoplasias Hepáticas/imunologia , Linfócitos T Reguladores/imunologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Estudos Transversais , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Resultado do Tratamento
4.
BMC Neurol ; 19(1): 148, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269910

RESUMO

BACKGROUND: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. METHODS: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. RESULTS: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. CONCLUSIONS: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.


Assuntos
Isquemia Encefálica/imunologia , Antígenos HLA-DR/sangue , Interleucina-6/sangue , Pneumonia/etiologia , Acidente Vascular Cerebral/imunologia , Proteínas da Fase Aguda , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/mortalidade , Proteínas de Transporte/sangue , Diabetes Mellitus , Feminino , Alemanha , Humanos , Tolerância Imunológica , Inflamação/complicações , Interleucina-10/sangue , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Pneumonia/mortalidade , Estudos Prospectivos , Espanha , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
5.
J Biol Regul Homeost Agents ; 33(3): 745-752, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184101

RESUMO

This study aimed to explore the effect of Sca-1+ bone marrow stromal stem cells (BMSCs) on lung ischemia reperfusion injury in mice. Five healthy Sprague-Dawley rats were selected to isolate and purify their Sca-1+ BMSCs using a Sca-1+ magnetic sorting kit in conjunction with whole bone marrow culture. In addition, 21 male C57BL/6J mice were divided into 3 groups (7 mice in each group), namely sham group (group A), I/R group (group B) and BMSCs group (group C). A pulmonary ischemia reperfusion injury model was established by ligating the left pulmonary portal vessel for 60 min and reperfusion for 240 min, after which the right pulmonary portal vessel was blocked to measure arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Subsequently, the mice were sacrificed to determine their superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the lung tissue. The histological changes were observed by light microscopy, while an enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in plasma expressions of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the mice. In addition, plasma expressions of TNF-α and B-cell lymphoma-2 (bcl-2) in the mice were detected by immunohistochemistry, while the apoptosis of transplanted lung cells was detected by a TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Compared with group A, group B showed a decreased level of PaO2 and SOD activity but an increased level of MDA content and MPO activity (P less than 0.01), indicating that group B had significant ischemia reperfusion injury compared to group A. In conclusion, BMSCs significantly reduced lung ischemia-reperfusion injury and improved lung function through their anti-oxidation, anti-inflammatory and anti-apoptosis properties.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Traumatismo por Reperfusão/terapia , Animais , Apoptose , Interleucina-10/sangue , Pulmão , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/sangue
6.
Cell Mol Biol Lett ; 24: 43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236121

RESUMO

Background: Impairment of the blood-brain barrier (BBB) could result in secondary cerebral edema and life-threatening pancreatic encephalopathy in patients with severe acute pancreatitis (SAP). Mesenchymal stem cells (MSCs) have been widely adopted in clinical research because of their pleiotropic functions. The aim of this study was to investigate the impact of MSCs on BBB permeability in SAP and the potential mechanisms driving these effects. Methods: Sprague-Dawley rats were randomly assigned to the control, SAP and SAP+MSCs groups. Pancreatic impairment was assessed. The serum levels of amylase, TNF-α and IL-10, expression levels of claudin-5, Bax, Bcl-2 and MMP-9, and the BBB permeability were measured. Endothelial cell apoptosis was evaluated. Results: SAP rats showed BBB impairment with increased permeability and secondary cerebral edema, which was confirmed using the Evans blue assay and the calculation of the brain dry/wet ratio. Treatment with MSCs decreased the serum levels of amylase and TNF-α, increased the serum levels of IL-10, attenuated the apoptosis of brain microvascular endothelial cells, upregulated claudin-5 expression and downregulated MMP-9 expression. This treatment attenuated the increased BBB permeability in SAP rats. Conclusions: MSCs attenuated the impairment of the BBB and decreased its permeability, producing protective effects in SAP rats.


Assuntos
Barreira Hematoencefálica/metabolismo , Transplante de Células-Tronco Mesenquimais , Pancreatite/metabolismo , Pancreatite/terapia , Doença Aguda/terapia , Amilases/sangue , Animais , Apoptose , Claudina-5/sangue , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Interleucina-10/sangue , Masculino , Metaloproteinase 9 da Matriz/sangue , Pancreatite/sangue , Permeabilidade , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
7.
Undersea Hyperb Med ; 46(1): 35-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31154683

RESUMO

Introduction: Diabetic foot ulcers are a frequent complication of diabetes and the first cause of non-traumatic lower limb amputation. They affect quality of life, restrict social productivity and generate a high economic burden for health care systems. Hyperbaric oxygen (HBO2) therapy is an adjunctive treatment option because it improves wound healing in the short term. However, its ability to modulate the pro- and anti-inflammatory balance and the hypoxic cell response in the clinical setting has not been fully described. Objective: To determine modifications in HIF-1α, NF-κB, IGFBP-3, and VEGF expression in wounds as well as circulating inflammatory cytokines in patients with diabetic foot ulcers subjected to HBO2. Materials and methods: We studied 17 ambulatory patients and one hospitalized patient with diabetic foot ulcers classified as Grade 3 or 4 according to the Wagner scale. All underwent HBO2 therapy. Tissue expression of HIF-1α, NF-κB, IGFBP-3, and VEGF was determined by immunohistochemistry. Plasma levels of adiponectin, IL-6, IFN-γ, IL-10 and IL-4 were measured by ELISA and chemiluminescence. Fibrosis and angiogenesis were determined by Masson's trichrome staining. Results: Ulcers in all patients healed after one month of HBO2, and none presented relapses at the one-year follow-up. At the beginning of treatment, HIF-1α and NF-κB expression was observed mainly in the nucleus, whereas these proteins were localized in the cytoplasm at the end of HBO2. There were significant modifications in VEGF expression after therapy, an increase in the plasma level of proinflammatory IL-6, and a decrease in that of IFN-γ. IGFBP-3 expression and plasma levels of adiponectin were increased at the end of HBO2. Increases in fibrosis and angiogenesis were also observed. Conclusion: These results suggest that adjuvant HBO2 modifies the proinflammatory balance related to the cellular response to hypoxia.


Assuntos
Adiponectina/metabolismo , Pé Diabético/metabolismo , Oxigenação Hiperbárica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , NF-kappa B/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Pé Diabético/terapia , Feminino , Hemoglobina A Glicada/análise , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-4/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade
8.
Mem Inst Oswaldo Cruz ; 114: e180571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116244

RESUMO

BACKGROUND: TcP21 is a ubiquitous secreted protein of Trypanosoma cruzi and its recombinant form (rP21) promotes parasite cell invasion and acts as a phagocytosis inducer by activating actin polymerisation in the host cell. OBJECTIVE: Our goal was to evaluate if the additional supplementation of rP21 during a prime/boost/challenge scheme with T. cruzi TCC attenuated parasites could modify the well-known protective behavior conferred by these parasites. METHODS: The humoral immune response was evaluated through the assessment of total anti-T. cruzi antibodies as well as IgG subtypes. IFN-γ, TNF-α and IL-10 were measured in supernatants of splenic cells stimulated with total parasite homogenate or rP21. FINDINGS: Our results demonstrated that, when comparing TCC+rP21 vs. TCC vaccinated animals, the levels of IFN-γ were significantly higher in the former group, while the levels of IL-10 and TNF-α were significantly lower. Further, the measurement of parasite load after lethal challenge showed an exacerbated infection and parasite load in heart and skeletal muscle after pre-treatment with rP21, suggesting the important role of this protein during parasite natural invasion process. MAIN CONCLUSION: Our results demonstrated that rP21 may have adjuvant capacity able to modify the cytokine immune profile elicited by attenuated parasites.


Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Doença de Chagas/imunologia , Proteínas de Protozoários/imunologia , Trypanosoma cruzi/imunologia , Vacinas Atenuadas/imunologia , Animais , Doença de Chagas/prevenção & controle , Modelos Animais de Doenças , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interferon-alfa/sangue , Interferon-alfa/imunologia , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-10/sangue , Interleucina-10/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose , Vacinas Atenuadas/administração & dosagem
9.
Pak J Biol Sci ; 22(3): 148-153, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30972985

RESUMO

BACKGROUND AND OBJECTIVE: Preeclampsia(PE) is adisordercharacterized byhypertensionandproteinuria. There is accumulating evidence that this is a disease of the endothelium. Angiogenic factors may be responsible for the regulation of placental vascular development. Clinicians cannot predict pre-eclampsia prior to the onset symptoms. An ideal bio-marker for pre-eclampsia prediction is during the first trimester. This study investigated the serum levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and the gene expressions of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and p53 in PE trying to find out potential bio-markers for prediction and diagnosis of PE. MATERIAL AND METHODS: A total of 100 female volunteers were involved in this study and their ages were ranged from 25-35 years. They were divided into three groups: Group (1) was 20 healthy non-pregnant women, group (2) was 20 pregnant women normal pregnancies and group (3) was 60 preeclamptic patients. The study participants were enrolled at the Department of Obstetrics and Gynaecology at Mansoura University Hospital, Mansoura, Egypt. The study was approved by the Research Ethics Committee (Faculty of Science, Al Azhar University, Egypt) approved on the March 15, 2014) all women gave written informed consent. Serum levels of CRP, IL-10 and TNF-α were evaluated, in addition to the gene expression of VEGF, eNOS and p53. RESULTS: Significant elevations in the serum levels of blood pressure, TNF-α and CRP were observed in PE patients. Additionally, the gene expression of VEGF, eNOS and P53 were down-regulated in preeclampsia. CONCLUSION: Elevated serum levels of TNFα and CRP, in addition to the down-regulation of eNOS may be used as good predictors for preeclampsia. The TNF-α and VEGF gene were recommended used as markers for PE to be added to routine testes of pregnant women.


Assuntos
Citocinas/sangue , Perfilação da Expressão Gênica , Pré-Eclâmpsia/sangue , Complicações na Gravidez/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Egito , Feminino , Humanos , Interleucina-10/sangue , Óxido Nítrico Sintase Tipo III/sangue , Pré-Eclâmpsia/diagnóstico , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/sangue , Proteína Supressora de Tumor p53/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
10.
Mediators Inflamm ; 2019: 2473164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944545

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.


Assuntos
Linfócitos B/metabolismo , Linfócitos B/patologia , Plaquetas/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Adulto , Ligante de CD40/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade
11.
Bull Exp Biol Med ; 166(6): 770-773, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028583

RESUMO

Plant lipid transfer proteins and homologues of the main birch pollen allergen Bet v 1 are involved in the development of allergic reactions of varying severity to plant foods and pollen. In this study, the sera from patients with tree and weed pollen allergies in the Moscow region were examined. The levels of IL-4, IL-5, IL-9, IL-10, IL-13, IL-17A, IFNγ, TNFα, and TNFß cytokines were determined in the sera of patients with specific IgE antibodies to Bet v 1 and Pru p 3 allergens. It was confirmed that patients with pollen allergy are often characterized by Th2 response of the immune system, though other mechanisms of allergy development occurred in some cases. The data obtained demonstrate the necessity of detailed analysis of the individual mechanism of allergic reactions and patient-centered approach to the personalized allergy treatment.


Assuntos
Antígenos de Plantas/imunologia , Proteínas de Transporte/imunologia , Imunoglobulina E/sangue , Proteínas de Plantas/imunologia , Rinite Alérgica Sazonal/sangue , Adulto , Antígenos de Plantas/química , Proteínas de Transporte/química , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Imunoglobulina E/genética , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-13/sangue , Interleucina-13/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Interleucina-4/sangue , Interleucina-4/imunologia , Interleucina-5/sangue , Interleucina-5/imunologia , Interleucina-9/sangue , Interleucina-9/imunologia , Linfotoxina-alfa/sangue , Linfotoxina-alfa/imunologia , Masculino , Pessoa de Meia-Idade , Moscou , Proteínas de Plantas/química , Medicina de Precisão , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Rinite Alérgica Sazonal/genética , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
12.
Mediators Inflamm ; 2019: 9483647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011288

RESUMO

CD4+ T-cells play crucial roles in the injured heart. However, the way in which different CD4+ T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4+ subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4+ T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α increased in both injured heart tissues and serum, while IFN-γ, IL-12P70, IL-2, IL-1ß, IL-18, TNF-α, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1α, RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN-γ, IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN-γ, IL-12P70, IL-2, IL-18, TNF-α, IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO-α were reduced, while IL-1ß and MIP-2 were elevated at day 14. IL-13 and MIP-1ß showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1ß, MCP-3, and GRO-α mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4+ T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Quimiocina CCL3/sangue , Quimiocina CCL3/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-13/sangue , Interleucina-13/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Infarto do Miocárdio/sangue , Traumatismo por Reperfusão Miocárdica/sangue
13.
BMC Neurol ; 19(1): 56, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954070

RESUMO

BACKGROUND: Dopaminergic neuronal loss begins years before motor symptoms appear in Parkinson disease (PD). Thus, reliable biomarkers for early diagnosis and prognosis of PD are an essential pre-requisite to develop disease modifying therapies. Inflammation-derived oxidative stress is postulated to contribute to nigrostriatal degeneration. We evaluated the role of selected serum immune mediators (IFNγ, TNFα, IL-10, and NOx) in PD progression and estimated their usefulness in preclinical diagnosis. METHODS: This case-control study recruited 72 PD patients with varying disease durations (< 1-year, n = 12 patients; 1-3 years, n = 30; > 3 years, n = 30) and 56 age- and gender-matched controls (26 with other neurological disorders as disease controls, and 30 healthy controls). Serum cytokine levels and NOx quantified using Sandwich Enzyme Linked Immunosorbent Assay kits, and the Griess test, respectively, were evaluated for diagnostic accuracy of optimal marker combinations by the CombiROC method. PD patients were clinically evaluated for motor and non-motor symptoms, and staged based on Hoehn and Yahr (H-Y) scale. RESULTS: A significant increase in serum IFNγ and IL-10 was observed in PD compared to healthy controls (p < 0.001). The Th1: Th2 (IFNγ: IL-10) cytokine ratio was higher in PD of 3-12 years compared with PD < 1 year (p < 0.001). Highest levels of NOx manifested during early PD (1-3 years) through a subsequent decline with disease duration. TNFα level was highest at PD onset. A low serum NOx level was associated with cognitive impairment (p = 0.002). The potential of using multi-biomarker panel, IFNγ, IL-10 and TNFα, for detection of PD onset was evident (sensitivity [SE] = 83.3%, specificity [SP] =80.4%, area under curve [AUC] = 0.868), while for early and late PD the multi-biomarker signature of IFNγ, IL-10 and NOx appeared to be more promising (SE = 93.3%, SP = 87.5%, AUC = 0.924). CONCLUSION: A Th1 cytokine-biased immune response predominates with PD progression. Both IFNγ and IL-10 are involved in disease severity. However, TNFα-mediated neurotoxicity appears to occur in early PD.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Óxido Nítrico/sangue , Doença de Parkinson/sangue , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Prognóstico , Fator de Necrose Tumoral alfa/sangue
14.
Hypertens Pregnancy ; 38(2): 96-104, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30821524

RESUMO

OBJECTIVE: We examined whether trimethylamine-N-oxide (TMAO) plays a role in endothelial dysfunction and hypertension in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia (PE).  Methods: Normal pregnant rats and RUPP rats were treated without or with 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) from gestational day 14.  Results: On day 19 of gestation, RUPP rats had higher plasma TMAO, impaired vasodilation and hypertension, decreased interleukin (IL)-10, increased superoxide production and proinflammatory cytokines in the aorta. All of which were reversed by DMD.  Conclusion: Increased circulating TMAO downregulates IL-10 and promotes vascular inflammation and oxidative stress, contributing to endothelial dysfunction and hypertension in PE.


Assuntos
Endotélio Vascular/fisiopatologia , Metilaminas/sangue , Pré-Eclâmpsia/sangue , Animais , Modelos Animais de Doenças , Endotélio Vascular/enzimologia , Feminino , Hexanóis , Inflamação/sangue , Interleucina-10/sangue , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pré-Eclâmpsia/enzimologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
15.
J Oral Sci ; 61(1): 53-60, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918217

RESUMO

The purpose of this study was to investigate the effects of vitamin D in rat models of chronic obstructive pulmonary disease (COPD) and periodontitis. Animals with both periodontitis and COPD, or with periodontitis only, were established. Once the animal model was established, experimental groups received intraperitoneal injections of 25-hydroxyvitamin D3 (25-OHD3) for 8 weeks, while control groups received refined peanut oil. After sacrifice, inflammatory status was examined in terms of the serum levels of receptor activator of the nuclear factor κB ligand (RANKL), tumor necrosis factor alpha (TNF-α) and interleukins (IL-1 and IL-10), as well as alveolar bone loss, forced expiratory volume (0.20) (FEV 0.20), and the ratio of FEV0.2 to forced vital capacity. The results showed that 25-OHD3 treatment significantly alleviated inflammation by decreasing the serum levels of RANKL, TNF-α and IL-1 and increasing that of IL-10, while reducing alveolar bone loss and slightly improving lung function. These findings suggest that vitamin D supplementation could be a new clinical approach for the treatment of COPD and periodontitis.


Assuntos
Calcifediol/farmacologia , Citocinas/sangue , Mediadores da Inflamação/metabolismo , Periodontite/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Animais , Calcifediol/administração & dosagem , Modelos Animais de Doenças , Injeções Intraperitoneais , Interleucina-1/sangue , Interleucina-10/sangue , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Ligante RANK/sangue , Ratos , Ratos Sprague-Dawley , Testes de Função Respiratória , Fator de Necrose Tumoral alfa/sangue
16.
Arch Pharm Res ; 42(4): 359-368, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30852731

RESUMO

Neuroinflammation plays a role in cancer chemotherapy-induced chronic pain. Thus far, most studies have focused on neuroinflammation suppression. However, there are limited reports of which factor is involved in the transition from acute inflammation to chronic inflammation, resulting in neuroinflammation and chronic pain. Here, we compared the inflammatory reaction and pain response induced by LPS and paclitaxel. LPS (0.5 mg/kg) or paclitaxel (2 mg/kg/day for 5 days) was administered intraperitoneally to mice, and mechanical allodynia was examined by von Frey test. LPS induced transient mechanical allodynia, whereas paclitaxel induced persistent mechanical allodynia. The CD86/CX3CR1 ratio remained unchanged due to CX3CR1 elevation following LPS injection, whereas the ratio was increased on day 1 after paclitaxel injection. LPS also increased CD45, CCL2, and CCL5 mRNA in the spinal cord and circulating pro- and anti-inflammatory cytokines 1 day after injection; however, the pattern was not consistent. Paclitaxel gradually increased inflammatory cytokines in the spinal cord. CX3CR1 might be involved in blocking the transition from acute pain to persistent pain in the LPS group. In addition, serum IL-4 and IL-10 elevation in the LPS group may be associated with chronic pain prevention. Therefore, targeting CX3CR1, IL-4, and IL-10 might be an alternative therapeutic strategy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Receptor 1 de Quimiocina CX3C/antagonistas & inibidores , Inflamação/tratamento farmacológico , Lipopolissacarídeos/antagonistas & inibidores , Neuralgia/tratamento farmacológico , Paclitaxel/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Receptor 1 de Quimiocina CX3C/metabolismo , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-10/antagonistas & inibidores , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-4/antagonistas & inibidores , Interleucina-4/sangue , Interleucina-4/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neuralgia/induzido quimicamente , Neuralgia/metabolismo , Paclitaxel/administração & dosagem , Fenótipo
17.
Medicine (Baltimore) ; 98(10): e14756, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30855474

RESUMO

To investigate the changes and significance of IL-37 in patients with sepsis.A total of 50 patients with sepsis between September 2016 and October 2017 at the intensive care unit (ICU) of the First Affiliated Hospital of Shihezi University School of Medicine were selected as the sepsis group, 30 age and sex-matched healthy controls were selected as the control group. The levels of IL-37 in serum were measured by enzyme-linked immunosorbent assay (ELISA) on day 1 and day 7 of the sepsis patients.The levels of serum IL-37 in the sepsis group on day 1 [(39.13 ±â€Š34.35)pg/mL] were significantly higher than that in the control group [(23.75 ±â€Š2.52)pg/mL] with significant difference (P <.05). The levels of IL-37 in the sepsis group after treatment [(30.57 ±â€Š11.01)pg/mL] on day 7 were obviously lower than that before treatment without statisticaly difference (P >.05). A correlation analysis showed that the levels of serum IL-37 and IL-1ß were positively correlated.The level of IL-37 observed in sepsis was found to correlate with the severity of the inflammatory reaction. IL-37 could be an important cytokine in the control of sepsis by suppressing the production of pro-inflammatory cytokines.


Assuntos
Interleucina-1/sangue , Sepse/sangue , Sepse/imunologia , Idoso , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Masculino , Estudos Prospectivos , Sepse/terapia , Resultado do Tratamento
18.
Cell Physiol Biochem ; 52(3): 565-579, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30897322

RESUMO

BACKGROUND/AIMS: During sepsis, an unchecked pro-inflammatory response can be detrimental to the host. We investigated the potential protective effect of amitriptyline (AT). METHODS: We used two murine models of sepsis: Cecal ligation and puncture and endotoxemia following LPS challenge. Aural temperatures were taken and cytokines quantified by cytometric bead assay. Lung injury was determined histologically and by protein determination in bronchoalveolar lavage fluid. Cell accumulation in the peritoneum was analyzed by flow cytometry, as well as cytokine production and p38-phosphorylation. Neutrophil chemotaxis was evaluated using an in vitro transwell assay. RESULTS: Our findings demonstrate that AT-treated septic mice have improved survival and are protected from pulmonary edema. Treatment with AT significantly decreased serum levels of KC and monocyte chemoattractant protein-1, as well as the accumulation of neutrophils and monocytes in the peritoneum of septic mice. Peritoneal IL-10 levels in septic mice were increased upon AT treatment. Direct treatment of septic mice with IL-10 recapitulated the effects of AT. Endotoxemic mice also exhibited enhanced IL-10 production upon AT-administration and peritoneal macrophages were identified as the ATinfluenced producers of IL-10. Treatment of these cells with AT in vitro resulted in increased p38-phosphorylation and IL-10 generation, whereas ceramide and p38 inhibition had the opposite effect. CONCLUSION: Altogether, AT treatment improved survival, increased IL-10 levels, and mitigated a pro-inflammatory response during sepsis. We conclude that AT is a promising therapeutic to temper inflammation during septic shock.


Assuntos
Amitriptilina/uso terapêutico , Sepse/tratamento farmacológico , Amitriptilina/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Ceramidas/farmacologia , Quimiocina CCL2/análise , Citocinas/análise , Modelos Animais de Doenças , Inflamação , Interleucina-10/sangue , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Neutrófilos/citologia , Neutrófilos/imunologia , Fosforilação/efeitos dos fármacos , Sepse/metabolismo , Sepse/mortalidade , Transdução de Sinais/efeitos dos fármacos , Taxa de Sobrevida , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Int J Rheum Dis ; 22(4): 677-685, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30729698

RESUMO

AIM: Dysregulated apoptosis has been implicated in autoimmune diseases. In the present study, we investigated the apoptosis-related cytokines and apoptosis in patients with primary antiphospholipid syndrome (pAPS). METHOD: We prospectively recruited 12 pAPS patients, 17 antiphospholipid antibody (APA)-positive systemic lupus erythematosus (SLE) patients without APS manifestations (APA+ SLE), 13 SLE patients with secondary APS (APS+ SLE) and 10 healthy controls (HCs). Plasma levels of soluble apoptosis-inducing ligands and cytokines, and the expression levels of apoptosis-inducing ligands in peripheral blood mononuclear cells, were determined. In addition, blood lymphocytes/monocytes apoptosis were determined in six pAPS patients and six HCs, using flow cytometric analysis of caspase 3, 8 and 9 activities. RESULTS: There was a trend toward higher plasma levels of soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL), interleukin-10 (IL-10) and TNF-α in pAPS patients when compared with HCs. We also observed higher plasma levels of IL-10 and TNF α in APA+ SLE and APS+ SLE patients when compared with HCs. However, there was no significant difference in blood lymphocytes/monocytes apoptosis between pAPS patients and HCs. CONCLUSION: There was a trend toward elevated plasma levels of sTRAIL, IL-10 and TNF-α, but no evidence for dysregulated apoptosis in pAPS patients.


Assuntos
Síndrome Antifosfolipídica/patologia , Proteínas Reguladoras de Apoptose/sangue , Apoptose , Citocinas/sangue , Linfócitos/patologia , Monócitos/patologia , Adulto , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/genética , Síndrome Antifosfolipídica/imunologia , Proteínas Reguladoras de Apoptose/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-10/sangue , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Estudos Prospectivos , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Fator de Necrose Tumoral alfa/sangue
20.
Appl Radiat Isot ; 146: 72-77, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30753988

RESUMO

OBJECTIVE: Intestinal injury is common after radiotherapy. We aim to investigate the effects of lactoferrin (Lf) on X-ray-induced intestinal injury in Balb/C mice. METHODS: In assessing animal survival, a total of 40 animals were assigned randomly to 8Gy group, 2 mg Lf+8Gy group, 4 mg Lf+8Gy group, and 6 mg Lf+8Gy group. Mice were administered with Lf intraperitoneally and exposed to single whole-body X-ray irradiation. Lf administration lasted for 3 days. Survival rate was compared among groups. For the observation of intestinal injury, a total of 60 animals were divided randomly into control group, 5Gy group, 2 mg Lf+5Gy group, and 4 mg Lf+5Gy group. Lf was administered once a day. Five mice in each group were randomly sacrificed at days 1, 3, and 9 after irradiation. Fasting blood was used to determine serum levels of pro-inflammatory cytokines IL-6 and TNF-α, and anti-inflammatorycytokine IL-10. Intestinal tissues were collected to examine histological changes and determine the protein expression levels of NF-κB, IKKα and IKKß. RESULTS: Mean survival time was 4.30 ± 1.34, 4.20 ± 0.71, 5.75 ± 2.44 and 6.70 ± 2.54 days in four groups, respectively, with significantly longer duration in 6 mg Lf+8Gy group than in the 8Gy group. Survival rate was significantly higher in 4 mg Lf+8Gy group and 6 mg Lf+8Gy group, compared with the 8Gy group. For intestinal histology, the radiation-induced injury was considerably improved in the 2 mg Lf+5Gy and 4 mg Lf+5Gy groups. Villus length and its ratio to crypt depth significantly increased in the two Lf intervention groups. Compared with 5Gy group, serum levels of IL-6 and TNF-α significantly decreased in the two Lf intervention groups at days 3 and 9. Furthermore, Lf significantly reduced the radiation-induced expression of IKKα/ß and NF-κB at day 3 and/or day 9. CONCLUSION: Lf extended the survival time of radiated mice and improved intestinal injury by decreasing inflammatory cytokines and downregulating NF-κB expression.


Assuntos
Mucosa Intestinal/lesões , Mucosa Intestinal/efeitos da radiação , Lactoferrina/administração & dosagem , Lesões Experimentais por Radiação/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Interleucina-10/sangue , Interleucina-6/sangue , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Protetores contra Radiação/administração & dosagem , Fator de Necrose Tumoral alfa/sangue
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