TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis

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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Cytokine TGF-β1, TNF-α, IFN-γ and IL‐6 Gene Polymorphisms and Localization of Premalignant Gastric Lesions in Immunohistochemically H. pylori-negative Patients

International Journal of Medical Sciences ◽

10.7150/ijms.60517 ◽

2021 ◽

Vol 18 (12) ◽

pp. 2743-2751

Author(s):

Anca Negovan ◽

Mihaela Iancu ◽

Florin Tripon ◽

Andrei Crauciuc ◽

Simona Mocan ◽

...

Keyword(s):

Gene Polymorphisms ◽

Gastric Lesions ◽

Tnf Α ◽

Ifn Γ ◽

H Pylori ◽

Tgf Β1

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Flow Cytometric Determination of Cellular Sources and Frequencies of Key Cytokine-Producing Lymphocytes Directed against Recombinant LACK and Soluble Leishmania Antigen in Human Cutaneous Leishmaniasis

Infection and Immunity ◽

10.1128/iai.69.5.3232-3239.2001 ◽

2001 ◽

Vol 69 (5) ◽

pp. 3232-3239 ◽

Cited By ~ 88

Author(s):

R. L. A. Bottrel ◽

W. O. Dutra ◽

F. A. Martins ◽

B. Gontijo ◽

E. Carvalho ◽

...

Keyword(s):

T Lymphocytes ◽

Cutaneous Leishmaniasis ◽

Ex Vivo ◽

Protozoan Parasite ◽

Recombinant Antigen ◽

Interleukin 4 ◽

Leishmania Braziliensis ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Ifn Γ

ABSTRACT Leishmaniasis, caused by infection with the protozoan parasiteLeishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-γ) production by several different sources, listed in order of contribution: CD4+ T lymphocytes, CD4−, CD8− lymphocytes, and CD8+ T lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN-γ and tumor necrosis factor alpha (TNF-α) than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human leishmaniasis involving Th1 CD4+ T lymphocytes (IFN-γ+ and IL-10−/IL-4−), Tc1 CD8+ T cells (IFN-γ+, and IL-10−/IL-4−), and a high frequency of TNF-α-producing lymphocytes. Moreover, it was determined that the recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA.

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Influence of the Interferon–Gamma (IFN–γ) and Tumor Necrosis Factor Alpha (TNF–α) Gene Polymorphisms in TB Occurrence and Clinical Spectrum

Tuberculosis - Current Issues in Diagnosis and Management ◽

10.5772/55099 ◽

2013 ◽

Cited By ~ 1

Author(s):

Marcia Quinhones Pires Lopes ◽

Raquel Lima de Figueiredo Teixeira ◽

Antonio Basilio de Miranda ◽

Rafael Santos ◽

Lizania Borges ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Interferon Gamma ◽

Gene Polymorphisms ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Ifn Γ ◽

Necrosis Factor

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The relationship between IFN-γ and TNF-α gene polymorphisms and brucellosis: Meta-analysis

Advances in Clinical and Experimental Medicine ◽

10.17219/acem/75869 ◽

2018 ◽

Vol 27 (12) ◽

pp. 1701-1709 ◽

Cited By ~ 2

Author(s):

Ebrahim Eskandari-Nasab ◽

Mehdi Moghadampour

Keyword(s):

Gene Polymorphisms ◽

Meta Analysis ◽

Tnf Α ◽

Ifn Γ ◽

The Relationship

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A Systematic Review and Meta-Analysis on Multiple Cytokine Gene Polymorphisms in the Pathogenesis of Periodontitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.713198 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xin Liu ◽

Hui Li

Keyword(s):

Systematic Review ◽

Publication Bias ◽

Gene Polymorphisms ◽

Inflammatory Responses ◽

Meta Analysis ◽

Cytokine Gene ◽

Protective Function ◽

Tnf Α ◽

Cytokine Gene Polymorphisms ◽

Ifn Γ

AimPeriodontitis is an inflammatory disease that destroys both soft and hard periodontal tissues. However, a complex periodontal cytokine network remains unclear. This systematic review explored multiple cytokine gene polymorphisms in the pathogenesis of periodontitis.Material and MethodsA systematic search was performed using the databases from previous publications, which indicated the association between cytokine polymorphisms and periodontitis pathogenesis. Meta-analysis was conducted using fixed or randomized models to calculate the significance of multiple cytokine polymorphisms. A total of 147 articles were analyzed with polymorphisms in 12 interleukins [Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4 and IL-13), Th17 (IL-1α, IL-1β, IL-6, and IL-17), and Treg cytokines (IL-10 and TGF-β)]. Doi plot was used to probe the occurrence of publication bias.ResultsThe polymorphisms of IL-2 and TNF-α of Th1 cytokine family may be associated with the pathogenesis or the prevention of periodontitis risk, while the polymorphism of IFN-γ is not related to periodontitis risk. The polymorphisms for IL-4 and IL-13 of Th2 cytokine family are not found to be associated with the pathogenesis of periodontitis. For the polymorphisms of the members of Th17 cytokine family, different IL-1α polymorphisms may have inverse actions in the pathogenesis of periodontitis. IL-1β is a noteworthy cytokine biomarker in periodontitis development and progression. IL-6 may have a protective function in the inflammatory responses of periodontitis, and IL-17 has a weak relationship the inflammatory responses. The polymorphisms for the members of Treg cell cytokines may have a protective function against periodontitis risk. LFK indexes show the major asymmetry due to publication bias.ConclusionIL-1β is a notable cytokine biomarker in periodontitis risk. Treg cytokines favor an anti-inflammatory and protective environment. Further data are needed to confirm the present conclusion due to publication bias.

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IFN-γ and TNF-α Gene Polymorphisms in Multiple Sclerosis Patients in Northwest Iran

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200505123443 ◽

2020 ◽

Vol 20 ◽

Author(s):

Mohammad Asgharzadeh ◽

Nima Najafi-Ghalehlou ◽

Behroz Mahdavi Poor ◽

Vahid Asgharzadeh ◽

Mahya Pourostadi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Responses ◽

Gene Polymorphisms ◽

Chi Square ◽

Specific Pcr ◽

Tnf Α ◽

Potential Risk Factors ◽

Chi Square Test ◽

Ifn Γ ◽

Multiple Sclerosis Patients

Background: Cytokines are polypeptides that play critical roles in immune responses. Gene polymorphisms occurring in the inflammatory cytokines are taking role in autoimmune diseases, including multiple sclerosis (MS), which may induce inappropriate immune responses. Objective: The aim of this study was to investigate the allelic and genotypic frequencies of interferon gamma gene (IFN-γ) at +874A/T locus and tumor necrosis factor (TNF-α) at+308A/G locus in MS patients of Azeri population. Methods: At first, a questionnaire was prepared for each of 240 healthy, non-relative, and 152 Azeri MS patients before obtaining the blood sample from all subjects. After DNA extraction, the frequency of alleles and genotypes of the IFN-γ and TNF-α genes at +874A/T and -308G/A loci, respectively, were determined by allele-specific PCR method. Finally, the frequencies were compared between control and MS patients by chi-square test (x2 -test) and p<0.05 was considered significant. Results: In the IFN-γ +874A/T gene single nucleotide polymorphism (SNP), the most allelic and genotypic frequencies in MS patients were the A allele, 55.26% (p=0.04) and the AT genotype, 52.63% (p=0.048). In healthy individuals, it was 65.42% for the A allele and 45.42% for the AA genotype. For the TNF-α 308 G/A SNP, the highest allelic and genotypic frequencies in MS patients were the G allele with 55.92% (p<0.001) and AG genotype with 61.84%, and in healthy subjects, the allelic and genotypic frequencies were 84.2% and 70.8% for the G allele and GG genotype, respectively. Conclusion: Head trauma, the infection with herpes virus and Mycoplasma pneumonia, frequent colds and high consumption of canned foods provide grounds for MS. The T allele in the IFN-γ gene (+874) and the genotypes of AA and AG at the TNF-α gene (-308) at the position-308 were considered as potential risk factors for MS. Therefore, the polymorphisms in cytokine genes and following changes in their expression levels can be effective in susceptibility to MS.

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Up-Regulation of Th1-Type Responses in Mucosal Leishmaniasis Patients

Infection and Immunity ◽

10.1128/iai.70.12.6734-6740.2002 ◽

2002 ◽

Vol 70 (12) ◽

pp. 6734-6740 ◽

Cited By ~ 203

Author(s):

Olívia Bacellar ◽

Hélio Lessa ◽

Albert Schriefer ◽

Paulo Machado ◽

Amélia Ribeiro de Jesus ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Cell Cultures ◽

Healthy Subjects ◽

Mononuclear Cells ◽

Transforming Growth Factor ◽

T Cell Response ◽

Cytokine Gene Expression ◽

Tnf Α ◽

Mucosal Leishmaniasis ◽

Ifn Γ

ABSTRACT The cytokine profile produced by peripheral blood mononuclear cells (PBMC) in response to leishmania antigens and the ability of interleukin-10 (IL-10) and transforming growth factor β (TGF-β) to modulate the immune response were evaluated in 21 mucosal leishmaniasis patients. Patients with mucosal disease exhibited increased gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) secretion and decreased IL-10 secretion compared to patients with classical cutaneous leishmaniasis. CD4+ Th1 cells were the main source of IFN-γ and TNF-α production in mucosal leishmaniasis patients. Evaluation of cytokine gene expression in PBMC of these patients showed that there was strong up-regulation of IFN-γ transcripts upon stimulation with leishmania antigen, in contrast to the baseline levels of IL-10 mRNA. IL-10 suppressed IFN-γ production by 48% in cell cultures from cutaneous leishmaniasis patients and by 86% in cell cultures from healthy subjects stimulated with purified protein derivative, whereas in similar conditions IL-10 suppressed IFN-γ production by 19% in cell cultures from mucosal leishmaniasis patients stimulated with leishmania antigen. TGF-β suppressed IFN-γ levels to a greater extent in healthy subjects than in mucosal leishmaniasis and cutaneous leishmaniasis patients. These data indicate that a poorly modulated T-cell response in mucosal leishmaniasis patients leads to production of high levels of proinflammatory cytokines, such as IFN-γ and TNF-α, as well as a decreased ability of IL-10 and TGF-β to modulate this response. These abnormalities may be the basis for the pathological findings observed in this disease.

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