scholarly journals Association of Interleukin-18 Gene Polymorphism with Susceptibility to Visceral Leishmaniasis in Endemic Area of Bihar, an Indian Population

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dinesh Kumar ◽  
Puja Tiwary ◽  
Jaya Chakravarty ◽  
Shyam Sundar

Interleukin-18 (IL-18) is a cytokine that mediates Th1 response by inducing interferon-gamma (IFN-γ) production in T cells and natural killer cells. Genetic polymorphisms in the IL-18 gene have been found to be associated with its expression in cancer, tuberculosis, HBV infection, and various other diseases. Lower plasma level of IL-18 in visceral leishmaniasis (VL) patients might be associated with polymorphisms in the regulating or coding region of the gene. Three single nucleotide polymorphisms (SNPs), rs1946519 (−656 G/T) and rs187238 (−137 G/C) in the promoter region and rs549908 (+105 A/C) in the codon region, were genotyped in 204 parasitological confirmed VL patients and 267 controls with no past history of VL. For each locus, polymerase chain reaction (PCR) followed by restriction digestion was performed. IL-18 expression in peripheral blood mononuclear cells (PBMC) collected from VL patients and controls was measured by quantitative real-time RT-PCR. Distribution of G allele at position −656(P<0.0001)and double haplotypes GGC/GGA(P=0.05)were found to be significantly associated with controls while genotypes TT(P<0.0001)and single haplotypes TGA(P=0.0002), with cases. The inheritance of G allele at the position −656 might be considered as a protective allele for VL.

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (2) ◽  
pp. 28-33
Author(s):  
T S Amyan ◽  
S G Perminova ◽  
L V Krechetova ◽  
V V Vtorushina

Study objective. To evaluate the efficacy of intrauterine administration of autologous peripheral blood mononuclear cells (PBMC) prior to embryo transfer in patients with recurrent implantation failures in IVF program. Materials and methods. The study enrolled 129 patients with recurrent implantation failures in an IVF programme. Group 1 - 42 patients who had intrauterine administration of autologous PBMC activated with hCG (Pregnyl 500 IU). Group 2 - 42 patients who had intrauterine administration of autologous PBMC without hCG activation. Group 3 (placebo) - 45 patients who had intrauterine administration of saline. Study results. In the hCG-activated PBMC group, the rates of positive blood hCG tests, implantation, and clinical pregnancy were significantly higher than the respective rates in the non-activated PBMC group and in the placebo group, both in a stimulated cycle and in an FET cycle (р≤0.05). Conclusion. Intrauterine administration of autologous PBMC prior to embryo transfer in an IVF/ICSI programme increases the efficacy of IVF program in patients with a history of recurrent implantation failures.


2015 ◽  
Vol 18 (2) ◽  
pp. 171 ◽  
Author(s):  
Jessica Cusato ◽  
Sarah Allegra ◽  
Amedeo De Nicolò ◽  
Lucio Boglione ◽  
Giovanna Fatiguso ◽  
...  

PURPOSE: Triple therapy for HCV-1 infection consists in boceprevir or telaprevir, ribavirin and PEG-interferon. Telaprevir is a P-glycoprotein substrate and it is metabolized by CYP3A4/5. No data have been published on intracellular penetration of telaprevir. We determined peripheral blood mononuclear cells (PBMCs) and trough plasma S and R telaprevir isomers concentrations; moreover, we evaluated the influence of some single nucleotide polymorphisms (SNPs) on these pharmacokinetic data after 1 month of triple therapy in humans. METHODS: Plasma and intracellular telaprevir concentrations were determined at the end of dosing interval (Ctrough) using ULPC-MS/MS validated methods; allelic discrimination was performed through real-time PCR. RESULTS: Median telaprevir Ctrough plasma concentrations were 2579 ng/mL and 2233 ng/mL for the pharmacologically more active S, and R, enantiomers, respectively, with median S/R plasma ratio of 1.11. In PBMC, the medians were 6863 ng/mL and 1096 ng/mL for S and R, respectively, with median S/R being 5.73. The PBMC:plasma ratio for S was 2.59 for R. Plasma ribavirin concentrations were directly correlated with plasma S-telaprevir concentrations. In linear regression analysis, only CYP24A1_rs2585428 SNP (p=0.003) and body mass index (p=0.038) were able to predict S-telaprevir PBMC concentrations. CONCLUSIONS: Our preliminary data could increase the understanding of mechanisms underlying telaprevir intracellular and plasma exposure, suggesting the implementation of pharmacogenetics in these drug kinetic studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


2014 ◽  
Vol 21 (4) ◽  
pp. 518-525 ◽  
Author(s):  
Hamid M. Niknam ◽  
Firoozeh Abrishami ◽  
Mohammad Doroudian ◽  
Mosayeb Rostamian ◽  
Maryam Moradi ◽  
...  

ABSTRACTVisceral leishmaniasis is a serious public health problem.Leishmania infantumis one of its causative agents. LCR1 is an immunogen fromL. infantum. Antibodies against this protein have been detected in visceral leishmaniasis patients. The aim of this study was to define the antibody and cellular immune responses against LCR1 in Iranian visceral leishmaniasis patients and recovered individuals. The LCR1 protein was produced in recombinant form. Antibody responses against this protein were studied in Iranian individuals with a recent history of visceral leishmaniasis. Responses of peripheral blood mononuclear cells to this protein were studied in Iranian individuals who had recovered from visceral leishmaniasis. Our data show that (i) there was an antibody response to LCR1 in each individual with a recent history of visceral leishmaniasis studied, (ii) there was neither a proliferative response nor production of gamma interferon (IFN-γ) or interleukin 10 in response to LCR1 by mononuclear cells from individuals who had recovered from visceral leishmaniasis, and (iii) individuals who have recovered from visceral leishmaniasis show ongoing immune responses long after recovery from the disease. These data show that there are no detectable cellular memory responses to LCR1 in Iranian individuals who have recovered from visceral leishmaniasis, while there are detectable antibody responses in patients with this disease. Our data suggest that LCR1 has potential applications for the diagnosis of leishmaniasis through antibody detection, while the application of LCR1 alone for induction of IFN-γ in individuals who recovered from this disease is not supported. The presence of long-lasting immune reactivities in individuals who recovered from the disease may show the necessity of extended medical surveillance for these individuals.


2009 ◽  
Vol 64 (5-6) ◽  
pp. 369-372 ◽  
Author(s):  
Xue-Feng Zhou ◽  
Lan Tang ◽  
Peng Zhang ◽  
Xiao-Ya Zhao ◽  
Hui-Fang Pi ◽  
...  

1Echinocystic acid (), an echinocystic acid saponin, 2, and four of its ester saponins, 3 - 6, obtained from the active fraction of Impatiens pritzellii var. hupehensis, an traditional Chinese medicine for rheumatoid arthritis, were investigated for their effects on lipopolysaccharide (LPS)-induced interleukin (IL)-18 in human peripheral blood mononuclear cells. Three of them, 1, 2 and 6, showed obvious activity to inhibit the production of IL-18, especially the ester saponins with a sugar chain at C-28, 6. Structure-activity relationships are discussed in brief


2015 ◽  
Vol 68 (6) ◽  
pp. 448-452 ◽  
Author(s):  
Ruijia Yan ◽  
Junjie Yang ◽  
Ping Jiang ◽  
Ling Jin ◽  
Jing Ma ◽  
...  

AimsTo explore the role of the suppressor of cytokine signalling 3 (SOCS3) gene in Graves’ ophthalmopathy (GO) patients.MethodsA case–control study was conducted in a Chinese Han population by recruiting 114 Graves’ disease (GD) patients with GO and 156 GD patients without GO. We determined SOCS3 mRNA and protein levels in Epstein–Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) from peripheral blood mononuclear cells (PBMCs) by quantitative real-time (QRT)-PCR analysis and western blot analysis. We also genotyped five single nucleotide polymorphisms (SNPs) in the SOCS3 locus (SOCS3 rs12952093, rs4969170, rs4969168, rs4969169 and rs2280148) in all 270 GD patients using ligase detection reaction and multiplex PCR analyses. QRT-PCR and western blot assays were then performed to compare SOCS3 mRNA and protein levels between the rs4969170 AA and GG genotype groups from 20 GO patients.ResultsBasal SOCS3 mRNA and protein expression levels were significantly increased in patients with GO (p<0.05). The SOCS3 rs4969170 AA genotype was strongly associated with GO (OR=3.5, 95% CI 1.6 to 7.5, p=0.001). The AA genotype carriers had significantly higher SOCS3 mRNA and protein levels than those with the GG genotype (p<0.05).ConclusionsPatients with GD who carry the AA genotype of the rs4969170 SNP in SOCS3 are more susceptible to the development of GO.


2005 ◽  
Vol 49 (8) ◽  
pp. 3228-3233 ◽  
Author(s):  
Hideo Kohka Takahashi ◽  
Hiromi Iwagaki ◽  
Dong Xue ◽  
Goutarou Katsuno ◽  
Sachi Sugita ◽  
...  

ABSTRACT Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E2 in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E2 and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E2 and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.


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