scholarly journals Endotoxin Modulates the Expression of Renal Drug Transporters in HIV-1 Transgenic Rats

2018 ◽  
Vol 21 (1s) ◽  
pp. 117s-129s ◽  
Author(s):  
Navaz Karimian Pour ◽  
Micheline Piquette-Miller
Keyword(s):  
Mrna Expression ◽  
Bacterial Infections ◽  
Drug Transporters ◽  
Serum Levels ◽  
Low Grade ◽  
Western Blots ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Associated Conditions ◽  
Ifn Γ

PURPUSE: Bacterial co-infections and low grade endotoxemia are common in HIV patients. Inflammation due to endotoxin or HIV may influence the expression and activity of transporters. Kidney transporters influence renal drug clearances including many antiretroviral agents. Our objective was to study the effect of endotoxin and HIV on the renal expression of drug transporters in an HIV-transgenic (HIV-Tg) rat model. These rats develop immune dysfunction and AIDS-associated conditions like humans. METHODS: Endotoxin or saline was administered intraperitoneally to HIV-Tg or wild type (WT) littermates and kidneys were collected 18 hours later. Expression of transporters and cytokines were measured by qRT-PCR and Western blots. Serum cytokine levels were measured by ELISA. RESULTS: Endotoxin induced serum levels of IL-6, TNF-α and IFN-γ in both HIV-Tg and WT animals. The basal mRNA expression of Oct2, Oct3, Octn1, Mate1, Urat1 and Ent1was significantly lower (33-60%) and the expression of Ent2 and Pept2 was significantly higher (33-45%) in HIV-Tg as compared to WT. While endotoxin significantly downregulated the mRNA expression of Mdra1 and Pept2 in both HIV and WT groups (69-78%), it imposed a significant reduction on the mRNA expression of Oct2, Oct3, Octn1, Mate1, Oat2, urat1, and Ent1 (54-83%) only in the WT group. Endotoxin significantly increased the mRNA expression of Pept1 (140%) in both WT and HIV groups. CONCLUSIONS: HIV and endotoxin each imposed alterations in the expression of many clinically important renal drug transporters although co-infection did not augment this effect. Viral and/or bacterial infections may impact the renal clearance of drug substrates in patients and could potentially be a source of drug-disease interactions.

scholarly journals Investigation of Immunopathological Processes Associated with the Development of Liver Fibrosis

2019 ◽  
Vol 1 (1) ◽  
pp. 53-58
Author(s):  
Эдвард Волчек
Keyword(s):  
Liver Fibrosis ◽  
Liver Diseases ◽  
Liver Stiffness ◽  
Serum Levels ◽  
Study Groups ◽  
Serum Samples ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Liver Elastography ◽  
Ifn Γ

The aim of this study was to determine the dependence of the course of liver fibrosis on the functional state of the immune system, in particular, on the imbalance of pro-inflammatory and anti-inflammatory immune reactions that are formed in patients during the development of the disease. The study included 30 patients with chronic liver diseases (18 patients with chronic hepatitis C (CHC) and 12 patients with alcoholic liver disease (ALD), 15 healthy individuals were the comparison group. Liver elastography (FibroScan) was used to evaluate liver stiffness and determine fibrosis stages according to METAVIR classification. The following cytokine levels were measured in the serum samples of the group: IL-1β, TNF-α, IL-6, IFN-γ, IL-2, IL-4, IL-8, VEGF and TGF-β. According to the data presented in this work, in patients with CHC and ALD, there was a statistically significant increase in serum levels of pro-inflammatory cytokines, namely: IL-1β, TNF-α, IFN-γ, IL-2, IL-6 and IL-8. Interestingly, elevated TGF-β values ​​were found in patients with CHC, but not in patients with ALD. Significantly lower concentrations of VEGF were observed in both study groups. There was also a significant decrease in serum IL-4 in patients with CHC, whereas in patients with ALD such a decrease was not statistically significant. Serum IL-1β content was approximately equally elevated in the early and late stages of fibrosis. A sharp rise in serum TNF-α levels occurred in the early stages of fibrosis. In the later stages, the rise in the level was replaced by a sharp fall. However, the serum levels of TNF-α in the later stages of liver fibrosis still significantly exceeded control values. The serum levels of IFN-γ in patients significantly exceeded control values without changes in different stages of fibrosis. Relatively high levels of serum IL-2 and IL-6 were noted only in the later stages of the disease. In both groups of patients, a clear dependence of serum levels of IL-8 on the stage of fibrosis was revealed. Analysis of the data allows us to conclude that immune mechanisms play a significant role in the pathogenesis of degenerative liver diseases. Therefore further studies of the mechanism and role of immune factors is required to explore possible diagnostic and therapeutic applications.

scholarly journals Prevalence of malaria and quantification of cytokine levels during infection in East Nile locality, Khartoum State: a cross-sectional study

F1000Research ◽  
2021 ◽  
Vol 8 ◽  
pp. 1529
Author(s):  
Hwida Barkat ◽  
Ahmed Bakheet Abd Alla ◽  
Ahmed Galander ◽  
Tagwa Salah ◽  
Tayseer Elfaki ◽  
...  
Keyword(s):  
Prevalence Rate ◽  
Malaria Infection ◽  
Public Health Problem ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Blood Film ◽  
Cross Sectional ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Background: The cytokines interferon gamma (IFN-γ), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF- α) play an important role in malaria infection. The aim of this study was to determine the prevalence of malaria and to evaluate cytokine responses to malaria infection in patients from the East Nile locality of Khartoum State. Methods: This study was carried out from May to July 2018 in the East Nile Locality, Khartoum State. Blood samples were collected from 384 randomly selected patients for blood film analysis. Of these, 39 were selected for cytokine level analysis (10 control and 29 patient samples), determined using enzyme-linked immunosorbent assays. Results: The malaria prevalence rate among 384 patients was 18.5%. Plasmodium falciparum was the most prevalent (13%), while the prevalence of Plasmodium vivax was 4.6%. The rate of mixed infection was 0.8%. There was a higher prevalence rate (22.7%) in males than females (15.6%). However, we found no significant correlation between cytokine levels and parasitemia in the study group. Nevertheless, our study demonstrated a significant correlation between cytokine levels and recurrent infections. Conclusions: Together, our data show that malaria remains a public health problem in East Nile locality with a high prevalence. Additionally, serum levels of IFN- γ and TNF- α were significantly higher in malaria-infected individuals compared to non-infecting individuals and cytokine levels were found to be correlated with recurrent malaria infection.

CD4+CD25- effector T cells from healthy controls and MS patients do not differ in mRNA expression of IFN-γ, IL-2, and TNF-α

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
A Hug ◽  
J Haas ◽  
A Viehöver ◽  
B Fritz ◽  
B Storch-Hagenlocher ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Effector T Cells ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ

IL-10-592 A/C Gene Polymorphism and Cytokine Levels are Associated with Susceptibility to Drug Resistance in Tuberculosis

2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  
Keyword(s):  
Serum Levels ◽  
World Health ◽  
Control Group ◽  
Drug Resistant ◽  
Nucleotide Polymorphisms ◽  
Genotype Frequencies ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Health Organization ◽  
And Function

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis

The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 354-361
Author(s):  
Gülay Okay ◽  
Meliha Meric Koc ◽  
Eray Metin Guler ◽  
Ayşegül Yabaci ◽  
Abdürrahim Kocyigit ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Cell Count ◽  
Cd4 T Cell ◽  
Positive Correlation ◽  
Hiv Rna ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Cd4 T Cell Count

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

scholarly journals Water Extract of Rubus coreanus Prevents Inflammatory Skin Diseases In Vitro Models

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1230
Author(s):  
Sumin Pyeon ◽  
Ok-Kyung Kim ◽  
Ho-Geun Yoon ◽  
Shintae Kim ◽  
Kyung-Chul Choi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Skin Diseases ◽  
Water Extract ◽  
Total Phenolic ◽  
Hacat Cells ◽  
Rubus Coreanus ◽  
Tnf Α ◽  
Ifn Γ ◽  
Inflammatory Skin

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by immune hypersensitivity reaction. The cause of AD is unclear, but its symptoms have a negative effect on quality of life; various treatment methods to alleviate these symptoms are underway. In the present study, we aimed to evaluate in vitro antioxidant and anti-inflammatory effects of Rubus coreanus water extract (RCW) on AD. Total phenolic compounds and flavonoid content of RCW were 4242.40 ± 54.84 mg GAE/g RCE and 1010.99 ± 14.75 mg CE/g RCW, respectively. RCW reduced intracellular reactive oxygen species level and increased the action of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-stimulated HaCaT cells. Moreover, mRNA expression of the pro-inflammatory cytokines, including TNF-α, interleukin-1β, and interleukin-6, was downregulated by RCW in the TNF-α/IFN-γ-stimulated cells. The levels of inflammatory chemokines (thymus- and activation-regulated chemokine; eotaxin; macrophage-derived chemokine; regulated on activation, normal T-cell expressed and secreted; and granulocyte-macrophage colony-stimulating factor) and intercellular adhesion molecule-1 were decreased in the TNF-α/IFN-γ-stimulated HaCaT cells after RCW treatment. Additionally, the mRNA expression levels of filaggrin and involucrin, proteins that form the skin, were increased by RCW. Furthermore, RCW inhibited the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway in the TNF-α/IFN-γ-stimulated HaCaT cells. Collectively, the present investigation indicates that RCW is a potent substance that inhibits AD.

scholarly journals Profile of IL-2, IL-4, IL-10, IFN- ? , TNF- ? and KC-like cytokines in pregnant bitches

2014 ◽  
Vol 66 (4) ◽  
pp. 1067-1072
Author(s):  
M.A.R. Feliciano ◽  
A.S.L. Silva ◽  
R.M. Crivelaro ◽  
M.E.F. Oliveira ◽  
L.N. Coutinho ◽  
...  
Keyword(s):  
Immune Response ◽  
Natural Killer ◽  
Serum Levels ◽  
Blood Samples ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pathological Pregnancy ◽  
English Bulldog

The aim of this study was to determine the profile of IL-2, IL-4, IL-10, IFN-γ, and TNF-α cytokines and KC-like cells (natural killer) in pregnant bitches, unpublished values for the species. A total of 27 females of the Shi Tzu, Pug, English Bulldog and French breeds, weighing 4-20kg and aged 4-6 years were used. Blood samples were collected from bitches during the anestrous and on the 2nd, 5th, 6th, 7th and 8th week of pregnancy. Serum levels of cytokines were measured by panel MILLIPLEX MAP (CCYTO-90K, MILLIPORE, Billerica, Massachusetts, USA) validated for dogs. Twenty four females showed physiological pregnancy and three bitches showed pathological pregnancy. There was no difference between cytokine values during anestrous and gestational weeks of bitches (P>0.05). However, it was possible to verify the physiological behavior of serum levels during modulation of immune response in the gestational process of animals. In animals with gestational disorders, abnormal values for IL-2, IL-4 and INF-y were noted. It was concluded that serum levels of cytokines evaluated in pregnant bitches can help the better understanding of physiological and pathological gestational processes and correlated immunology in this species.

scholarly journals Trifluorobenzamidine prevents allergic rhinitis by regulating IgE, IL-4 and IL-5 in T-cells

2020 ◽  
Vol 19 (5) ◽  
pp. 1023-1029
Author(s):  
Yongbo Zhang ◽  
Zhuo Wu ◽  
Yihui Yang ◽  
Lu Ding
Keyword(s):  
Allergic Rhinitis ◽  
Serum Levels ◽  
Eosinophil Infiltration ◽  
Spleen Weight ◽  
Caspase 1 ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Enzymelinked Immunosorbent Assay ◽  
Inhibitory Potential ◽  
New Treatment

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

scholarly journals Correlations of Expression Levels of a Panel of Genes (IRF5, STAT4, TNFSF4, MECP2, and TLR7) and Cytokine Levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, and TNF-α) with Systemic Lupus Erythematosus Outcomes in Jordanian Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Amal H. Uzrail ◽  
Areej M. Assaf ◽  
Shtaywy S. Abdalla
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Cardiovascular Damage ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.

scholarly journals Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis

2013 ◽  
Vol 39 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Beatriz Lima Alezio Muller ◽  
Daniela Maria de Paula Ramalho ◽  
Paula Fernanda Gonçalves dos Santos ◽  
Eliene Denites Duarte Mesquita ◽  
Afranio Lineu Kritski ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Pulmonary Tuberculosis ◽  
Gene Polymorphisms ◽  
Serum Levels ◽  
Acute Inflammatory Response ◽  
Reactive Protein ◽  
Antituberculosis Treatment ◽  
Tnf Α ◽  
Referral Hospitals ◽  
Ifn Γ

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis.METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts.RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels.CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment.

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