interleukin-8 has been researched along with Tuberculosis--Pulmonary* in 41 studies
1 review(s) available for interleukin-8 and Tuberculosis--Pulmonary
1 trial(s) available for interleukin-8 and Tuberculosis--Pulmonary
40 other study(ies) available for interleukin-8 and Tuberculosis--Pulmonary
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Sex-Dependent Differential Expression of Lipidic Mediators Associated with Inflammation Resolution in Patients with Pulmonary Tuberculosis.
There is a sex bias in tuberculosis's severity, prevalence, and pathogenesis, and the rates are higher in men. Immunological and physiological factors are fundamental contributors to the development of the disease, and sex-related factors could play an essential role in making women more resistant to severe forms of the disease. In this study, we evaluated sex-dependent differences in inflammatory markers. Serum samples were collected from 34 patients diagnosed with pulmonary TB (19 male and 15 female) and 27 healthy controls (18 male and 9 female). Cytokines IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα, and GM-CSF, and eicosanoids PGE2, LTB4, RvD1, and Mar1 were measured using commercially available immunoassays. The MDA, a product of lipidic peroxidation, was measured by detecting thiobarbituric-acid-reactive substances (TBARS). Differential inflammation patterns between men and women were observed. Men had higher levels of IL6, IL8, and TNFα than women. PGE2 and LTB4 levels were higher in patients than healthy controls, but there were no differences for RvD1 and Mar1. Women had higher RvD1/PGE2 and RvD1/LTB4 ratios among patients. RvD1 plays a vital role in resolving the inflammatory process of TB in women. Men are the major contributors to the typical pro-inflammatory profile observed in the serum of tuberculosis patients. Topics: Dinoprostone; Eicosanoids; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukotriene B4; Male; Tuberculosis; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2022 |
Possible relation between expression of circulating microRNA and plasma cytokine levels in cases of pulmonary tuberculosis.
Tuberculosis (TB) is a life-threatening infection and early diagnosis is critical for treatment and prevention of transmission. There is evidence of correlation between miRNA expression and cytokine regulation during TB infection. The aim of this study was to determine the relationship between expression levels of miRNAs in plasma and cytokine levels as a potential biomarker for genetic predisposition and/or early diagnosis of TB infection.. The expression levels of 86 miRNAs were examined in plasma samples of 44 TB patients and 44 healthy controls by qRT-PCR using BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation, South San Francisco, CA, USA) system. The levels of plasma TNF-α, IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, and IL-12/P40 were examined with ELISA.. We identified dysregulation of 18 miRNAs which included upregulation of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-100-5p, miR-106b-5p, miR-128-3p, miR-133a-3p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-205-5p, miR-210-3p, and miR-296-5p, and downregulation of miR-15b-5p, miR-16-5p, and miR-25-3p in plasma samples of patients with pulmonary TB (p < 0.05). A significant correlation between the expression levels of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-15b-5p, miR-100-5p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-210-3p and cytokine levels of TNF-α, IFN-γ, IL-1β, IL-8 and IL-10 was identified (p < 0.05).. We demonstrated that altered expression levels of plasma miRNAs consistent with immunological response have the potential to serve as non-invasive biomarkers for early diagnosis of pulmonary TB. Additional investigations with larger sample sizes will be required to confirm our findings and to determine if miRNAs can be possible targets for TB management strategies. Topics: Biomarkers; Circulating MicroRNA; Cytokines; Gene Expression Profiling; Humans; Interleukin-10; Interleukin-8; MicroRNAs; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2022 |
Toll like receptor (2 and 4) expression and cytokine release by human neutrophils during tuberculosis treatment-A longitudinal study.
Host innate immune responses to tuberculosis are poorly explored. Recent findings emphasize the importance of innate cells in working against Mycobacterium tuberculosis, the etiologic agent of this deadly disease. In this study we have tried to learn the role of neutrophils in building up immunity against this pathogen during therapy. We isolated neutrophils from peripheral blood of healthy volunteers and pulmonary tuberculosis patients at different phases of their treatment and cultured them withtoll like receptor ligands overnight. Toll like receptor 2 and 4 expression on neutrophils was analyzed using flow cytometry. The supernatants were used to measure cytokines. We found that in tuberculosis patients, expression of TLR2, a proven receptor of Mycobacterium tuberculosis on neutrophils, was increased throughout the duration of therapy (measured at diagnosis, second month and sixth month of therapy). This demonstrates that TLR2 expression is altered as a result of treatment, but not TLR4. Also, the chemokines IL-8 and MIP1α showed a 'dip and raise' fashion as the therapy proceeded. Even though the increase in the pro-inflammatory cytokine secretion by neutrophils seen at the end of therapy is not as expected, it definitely increases our understanding on the function of these cells during TB disease and its resolution and opens new direction in neutrophil research. Topics: Adult; Chemokine CCL3; Cytokines; Female; Fluorescence; Humans; Interleukin-8; Longitudinal Studies; Male; Neutrophils; Toll-Like Receptor 2; Toll-Like Receptor 4; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Young Adult | 2021 |
The Intracellular Growth of
Diabetes mellitus, a metabolic disease characterized by hyperglycemia and poor glucose control, is a risk factor for Topics: Adult; Aged; Case-Control Studies; Cell Survival; Diabetes Mellitus, Type 2; Female; Gene Expression; Glucose; Humans; Hyperglycemia; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Lipoproteins; Male; Middle Aged; Monocytes; Mycobacterium tuberculosis; Primary Cell Culture; Toll-Like Receptor 2; Toll-Like Receptor 4; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2019 |
Serum levels of chemokines IP-10, IL-8 and SDF-1 serve as good biomarkers for diabetes-tuberculosis nexus.
Inflammation has long been identified as an essential component of both Type-2 diabetes and tuberculosis. Chemokines are low molecular weight proteins which play an important role in both inflammation (diabetes) and immunity (tuberculosis).. In this study, we measured the serum levels of IP-10, IL-8 and SDF-1 in subjects with Normal Glucose Tolerance (NGT-TB. While IP-10 levels were significantly reduced in TB. Altered serum chemokine levels can alter anti-TB immunity in diabetes patients and can fuel DM-TB nexus. Topics: Adult; Biomarkers; Case-Control Studies; Chemokine CXCL10; Chemokine CXCL12; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Signal Transduction; Tuberculosis, Pulmonary; Young Adult | 2018 |
Impaired toll like receptor 9 response in pulmonary tuberculosis.
Innate immune responses are important in susceptibility to pulmonary tuberculosis (TB). In order to test the hypothesis that Toll-like receptor (TLR) 2 function would be abnormal in patients with active pulmonary TB we compared the cytokine responses of peripheral blood mononuclear cells (PBMC) to innate immune ligands in a case-control study.. PBMC from 19 untreated pulmonary TB patients, 17 healthy controls, and 11 treated pulmonary TB patients, were cultured for 24h with TLR 2 ligand (PAM-CSK) and other TLR ligands (muramyl dipeptide, flagellin, lipopolysaccharide (LPS), CpG oligodeoxynucleotide (CpG-ODN)). Interleukin-8 (IL-8) was estimated in the supernatant by ELISA. Messenger RNA expression for inflammatory cytokines was quantitated using real time PCR.. The important findings were (1) reduced PBMC secretion of IL-8 in response to all ligands in active TB; (2) normal to increased PBMC secretion of IL-8 in response to all ligands except CpG ODN (TLR 9 ligand) in TB patients who had recovered; (3) absence of difference in mRNA expression for a consortium of inflammatory pathway genes between healthy controls, active pulmonary tuberculosis and treated pulmonary tuberculosis patients.. There was a generalized post-translational suppression of the IL-8 response to innate immune ligands in active TB. There appears to be a defect of TLR 9 signaling in patients with tuberculosis, the nature of which needs to be further explored. Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adolescent; Adult; Female; Flagellin; Humans; Immunity, Innate; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Oligodeoxyribonucleotides; Signal Transduction; Toll-Like Receptor 9; Tuberculosis, Pulmonary | 2017 |
TLR stimulation of human neutrophils lead to increased release of MCP-1, MIP-1α, IL-1β, IL-8 and TNF during tuberculosis.
Neutrophils inform and shape immune responses. Toll-like receptors (TLRs) play an essential part in the perception of microbes and shape the complex host responses that occur during infection. The TLRs present on neutrophils play an indispensable role in neutrophil mediated pathogen recognition and elimination. This study was done to identify the role of significant TLRs in immune responses leading to differences in cytokine/chemokine release following stimulation. We evaluated the concentrations of various significant cytokines (IL-1β, TNF, MIP-1α, MCP-1 and IL-8) secreted by neutrophils from healthy donors and pulmonary tuberculosis patients following TLR ligand stimulation. TLR stimulation increased the release of such cytokines in both the groups. Thus it is noted that TLR stimulation of neutrophils definitely lead to increased cytokine response. Also, the release of all the studied cytokines are found to be greatly increased in patient neutrophils, affirming that neutrophils undergo secretory level modifications during tuberculosis infection. Topics: Adult; Cells, Cultured; Chemokine CCL2; Chemokine CCL3; Female; Humans; Interleukin-1beta; Interleukin-8; Male; Neutrophils; Toll-Like Receptors; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Up-Regulation; Young Adult | 2016 |
Reduced Phagocytic Capacity of Blood Monocyte/Macrophages in Tuberculosis Patients Is Further Reduced by Smoking.
Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p<0.01] took up FITC-dextran after 2h compared to non-smoking TB subjects [71.62% (69.2-74.1)] and healthy cases [97.45% (95.9-99.1). Phagocytic capacity was inversely correlated with cigarette smoking as measured by pack years (r=-0.73, p<0.001). The serum levels of TNF-a and CXCL-8 were significantly higher in the TB patients who smoked compared to the TB non-smoker group (p<0.001, p<0.01 respectively). Blood monocytes/macrophages from TB patients have reduced phagocytic capacity which is further reduced in TB patients who smoke. Smoking enhanced serum levels of TNF-a and CXCL-8 suggesting a greater imbalance between the proinflammatory and anti-inflammatory factors in these patients. Topics: Female; Humans; Interleukin-8; Macrophages; Male; Middle Aged; Monocytes; Phagocytosis; Smoking; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2016 |
HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis.
We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB).. A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo.. In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6-15.1) vs 3.6(3.6-3.6) pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001), severity-score (rs +0.317, P = 0.004), and fever and hospitalization durations (rs +0.407, P<0.001). IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan.. In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control. Topics: Adult; Antigens, Neoplasm; Female; Gene Expression Regulation, Bacterial; HIV; HMGB1 Protein; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Mitogen-Activated Protein Kinases; Signal Transduction; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2016 |
Expression of inhibitory regulators of innate immunity in patients with active tuberculosis.
Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. Toll-like-receptors (TLRs) are important for the recognition of the causative agent Mycobacterium tuberculosis. Negative regulation of TLRs is necessary to control deleterious inflammatory damage, but could provide a means of immune evasion by M. tuberculosis as well.. To obtain insight in the extent of expression of inhibitory regulators of immunity in patients with active TB, peripheral-blood-mononuclear-cells (PBMCs) and plasma were obtained from 54 TB patients and 29 healthy blood donors from Chittagong, Bangladesh. Bilateral alveolar macrophages were obtained from an infected versus a contralateral normal lung segment of 9 patients. Statistical analyses were performed using Mann-Whitney U and Wilcoxon matched pairs testing. Correlations were calculated using the Spearman rho test.. PBMCs harvested from TB patients demonstrated increased mRNA expression of IL-1-receptor-associated-kinase-M, suppressor-of-cytokine-signalling-3 and Toll-interacting-protein. Flow cytometry revealed enhanced expression of IL-1-receptor-like-1 (ST2) on lymphocytes. Plasma soluble ST2 was elevated in patients with TB and correlated with established TB biomarkers, most strongly with soluble interleukin-2 receptor subunit α and interleukin-8. Alveolar macrophage mRNA expression of negative TLR regulators did not differ between the infected and contralateral lung side.. These results show enhanced expression of distinct negative regulators of innate immunity in PBMCs of patients with TB and identify plasma soluble ST2 as a potential novel biomarker for TB disease activity. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bangladesh; Female; Flow Cytometry; Humans; Immunity, Innate; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Mycobacterium tuberculosis; Toll-Like Receptors; Tuberculosis, Pulmonary; Young Adult | 2015 |
Neutrophils from pulmonary tuberculosis patients show augmented levels of chemokines MIP-1α, IL-8 and MCP-1 which further increase upon in vitro infection with mycobacterial strains.
Neutrophils being innate cells initiate the immune defence against mycobacteria by sending signals to other immune cells. Chemokines being the vital link in signaling processes, it is of interest to study their secretion by neutrophils as a response to tuberculosis infection. The levels of various chemokines (MIP-1α, MCP-1, IL-8 and IP-10) and chemokine receptors (CXCR1, CXCR2 and CCR1) in neutrophils from healthy individuals and pulmonary tuberculosis patients were studied following infection with Mycobacterium tuberculosis strains (clinical--S7 and S10 and laboratory--H37Rv). The release of MIP-1α, IL-8 and MCP-1 is found to be greatly increased in patient neutrophils. Mycobacterial strains differentially influenced neutrophils affecting the release of chemokines to different extent. H37Rv significantly increased the release of MIP-1α and IL-8 in both normals and tuberculosis patients, while S10 up regulated only the release of MIP-1α in patients. Thus, during tuberculosis, neutrophils undergo functional alteration to combat infection. While H37Rv is greatly recognized by neutrophils and triggers the release of chemokines, clinical strains by some means try to suppress immune activation of neutrophils in their favor. Topics: Adult; Chemokine CCL2; Chemokine CCL3; Female; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Interleukin-8; Male; Middle Aged; Mycobacterium tuberculosis; Neutrophils; Primary Cell Culture; Receptors, CCR1; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Signal Transduction; Tuberculosis, Pulmonary | 2014 |
NF-κB repressing factor downregulates basal expression and mycobacterium tuberculosis induced IP-10 and IL-8 synthesis via interference with NF-κB in monocytes.
Our previous study showed NF-κB repressing factor (NKRF) downregulates IP-10 and IL-8 synthesis in the peripheral blood mononuclear cells and alveolar macrophages of TB patients with high bacterial loads. However, the mechanism underlying the repressive effect of NKRF is not fully understood.. The levels of IP-10, IL-8 and NKRF were significantly up-regulated in THP-1 cells treated with heated mycobacterium tuberculosis (H. TB). NKRF inhibited NF-κB-mediated IP-10 and IL-8 synthesis and release induced by H. TB. The repressive effect of NKRF is mediated via interference with NF-κB (p65) binding and RNA polymerase II recruitment to promoter sites of IP-10 and IL-8.. We have elucidated that direct contact with MTb induces IP-10, IL-8 and a concomitant increase in NKRF in THP-1 cells. The up-regulated NKRF serves as an endogenous repressor for IP-10 and IL-8 synthesis to hinder host from robust response to MTb infection. Topics: Cell Line; Chemokine CXCL10; Down-Regulation; Humans; Interleukin-8; Monocytes; Mycobacterium tuberculosis; Promoter Regions, Genetic; Repressor Proteins; RNA Polymerase II; Transcription Factor RelA; Tuberculosis, Pulmonary | 2014 |
Early secreted antigenic target of 6 kDa (ESAT-6) protein of Mycobacterium tuberculosis induces interleukin-8 (IL-8) expression in lung epithelial cells via protein kinase signaling and reactive oxygen species.
Early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis is critical for the virulence and pathogenicity of M. tuberculosis. IL-8, a major chemotactic cytokine for neutrophils and T lymphocytes, plays important roles in the development of lung injury. To further understand the role of ESAT-6 in lung pathology associated with tuberculosis development, we studied the effects of ESAT-6 on the regulation of IL-8 expression in lung epithelial cells. ESAT-6 induced IL-8 expression by increasing IL-8 gene transcription and mRNA stability. ESAT-6 induction of IL-8 promoter activity was dependent on nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) binding and sensitive to pharmacological inhibition of PKC and ERK and p38 MAPK pathways. ESAT-6 activated ERK and p38 MAPK phosphorylation and rapidly induced reactive oxygen species (ROS) production. Dimethylthiourea but not mannitol inhibited IL-8 induction by ESAT-6, further supporting the involvement of ROS in the induction of IL-8 expression. Exposure of mice to ESAT-6 induced localized inflammatory cell aggregate formation with characteristics of early granuloma concomitant with increased keratinocyte chemoattractant CXCL1 staining in bronchiolar and alveolar type II epithelial cells and alveolar macrophages. Our studies have identified a signal transduction pathway involving ROS, PKC, ERK, and p38 MAPKs and NF-κB and AP-1 in the ESAT-6 induction of IL-8 expression in lung epithelial cells. This has important implications for the understanding of lung innate immune responses to tuberculosis and the pathogenesis of lung injury in tuberculosis. Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Cell Line, Tumor; Epithelial Cells; Gene Expression Regulation; Humans; Interleukin-8; Lung; Macrophages, Alveolar; MAP Kinase Signaling System; Mice; Mycobacterium tuberculosis; NF-kappa B; Promoter Regions, Genetic; Protein Kinases; Reactive Oxygen Species; Respiratory Mucosa; Transcription Factor AP-1; Transcription, Genetic; Tuberculosis, Pulmonary | 2013 |
Mycobacterium bovis bacilli Calmette-Guerin regulates leukocyte recruitment by modulating alveolar inflammatory responses.
Leukocyte migration into the epithelial compartment is an important feature in the active phase of mycobacterial infections. In this study, we used the Transwell model to investigate the mechanisms behind mycobacteria-induced leukocyte recruitment and investigated the role of TLR2 and TLR4 in this process. Infection of epithelial cells resulted in significantly increased secretion of the neutrophil chemotactic CXCL8 and IL-6, but no secretion of monocyte chemotactic CCL2 or TNF-α was observed. In contrast to epithelial response, mycobacteria-infected neutrophils and monocytes secreted all these cytokines. Corresponding with epithelial cytokine response, mycobacterial infection of the epithelial cells increased neutrophil diapedesis, but decreased monocyte recruitment. However, monocyte recruitment towards mycobacteria infected epithelial cells significantly increased following addition of neutrophil pre-conditioned medium. Mycobacterial infection also increases alveolar epithelial expression of TLR2, but not TLR4, as analyzed by flow cytometry, Western blotting and visualized by confocal microscopy. Blocking of TLR2 inhibited neutrophil recruitment and cytokine secretion, while blocking of TLR4 had a lesser effect. To summarize, we found that primary alveolar epithelial cells produced a selective TLR2-dependent cytokine secretion upon mycobacterial infection. Furthermore, we found that cooperation between cells of the innate immunity is required in mounting proper antimicrobial defence. Topics: Cell Line; Cell Movement; Gene Expression Regulation; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Mycobacterium bovis; Neutrophils; Pulmonary Alveoli; Toll-Like Receptor 2; Toll-Like Receptor 4; Transendothelial and Transepithelial Migration; Tuberculosis, Pulmonary | 2012 |
Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model.
An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor alpha (TNFalpha)-neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model.. Cynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6-8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF-neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55-TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison.. Administration of TNF-neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin-12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria-induced interferon-gamma production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes.. These findings have important clinical implications for determining the mechanism of TNF neutralization-related tuberculosis. Topics: Acute Disease; Adalimumab; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Chemokine CCL4; Chronic Disease; Disease Models, Animal; Granuloma; Immunosuppression Therapy; Interferon-gamma; Interleukin-12; Interleukin-2; Interleukin-8; Macaca fascicularis; Mycobacterium tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2010 |
[Immunological parameters in the assessment of the activity of a specific process in Mycobacterium tuberculosis-infected children and patients with intrathoracic lymphatic tuberculosis].
The data of a comprehensive study of 86 children aged 6 to 14 years, who were examined and treated at the Research Institute of Phthisiology for various manifestations of tuberculous infection: 25.6% with infected Mycobacterium tuberculosis with varying specific sensitization; 34.9% with minor forms of intrathoracic lymphatic tuberculosis (ITLT), 39.5% with disseminated processes into the intrathoracic lymph nodes, are analysed. Of the greatest informative value in the determination of the activity of tuberculous infection are RM V, VI, VII, and VIII dilutions in combination with immunological parameters of specific immunity: blast transpormation reaction (BTR) to PPD, a complex of serological reactions, IL-8, and lysosomal cationic test (LCT). Most children with ITLT showed a significant cellular response to PPD in the BTR test. It should be noted that on admission to the clinic, neutrophilic granulocytes were functionally inadequate in all the children as shown by LCT. The currently available immunological tests used in combination with the existing methods in the diagnosis of ITLT adequately evaluate the activity of tuberculous infection in children. Topics: Adolescent; Antibodies, Bacterial; Antibody Formation; BCG Vaccine; Child; Humans; Immunity, Cellular; Immunologic Tests; Infant, Newborn; Interleukin-8; Mycobacterium tuberculosis; Neutrophils; Radiography, Thoracic; Tomography, X-Ray Computed; Tuberculin Test; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary | 2009 |
Engagement of Toll-like receptor 2 on CD4(+) T cells facilitates local immune responses in patients with tuberculous pleurisy.
Although it has been recognized that Mycobacterium tuberculosis contains large amounts of Toll-like receptor 2 (TLR2) ligands, their direct effects on CD4(+) T cells and the clinical implications have not been determined.. With the recent finding that activated CD4(+) T cells express TLR2 as a costimulatory receptor, we hypothesized that M. tuberculosis and its components may directly affect CD4(+) T cells by engaging TLR2, thus facilitating the expansion and function of these lymphocytes in tuberculous pleura.. Our results indicate that CD4(+) T cells from the pleural fluid and peripheral blood of patients with tuberculosis show significantly increased TLR2 expression, compared with those from healthy donors. TLR2 ligand activity was also significantly higher in the tuberculous pleural fluid than in the serum from healthy donors or patients with pulmonary tuberculosis. M. tuberculosis TLR2 ligands, 19-kDa lipoprotein, and live bacillus Calmette-Guérin all modulated cytokine production (interferon gamma and interleukin 17), cellular proliferation, survival, and migration of CD4(+) T cells isolated from pleural fluid and activated with anti-CD3 and anti-CD28.. These data indicate that direct interaction between M. tuberculosis TLR2 ligands and CD4(+) T cells facilitated local CD4(+) T cell immune responses in patients with tuberculous pleurisy. Topics: Adult; Case-Control Studies; CD4-Positive T-Lymphocytes; Cell Movement; Cells, Cultured; Female; Gene Expression Regulation; Humans; Interleukin-8; Male; Middle Aged; Mycobacterium tuberculosis; Toll-Like Receptor 2; Tuberculosis, Pleural; Tuberculosis, Pulmonary; Young Adult | 2009 |
[Some regularities of an immune response in patients with pulmonary tuberculosis and drug-resistant Mycobacterium strains].
Clinical and immunological studies were conducted in 62 patients with infiltrative pulmonary tuberculosis and 53 with disseminated one. As drug resistance and viability of mycobacteria increased, an immune response was found to develop as the humoral type and cellular immunity was suppressed. A more marked reduction in the activity of T helper cells type 1 of an immune response and the neutrophilic granulocytic system was revealed in patients with disseminated pulmonary tuberculosis. The maximum suppression of cell immunity was found in patients with multidrug-resistant mycobacterial strains. The observed changes in an immune response and in the production of cytokines (IL-2, IL-8) are informative signs correlating with deterioration of a specific process. Mycobacterial drug resistance and its suppressed cell immunity make chemotherapy policy difficult. The findings identify patients with mycobacterial drug resistance and high viability as a group of priority in the context of immunomodulator therapy. Topics: Adult; Antibody Formation; Antitubercular Agents; Data Interpretation, Statistical; Drug Resistance, Multiple, Bacterial; Humans; Immunity, Cellular; Immunologic Factors; Interleukin-2; Interleukin-8; Mycobacterium tuberculosis; Neutrophils; T-Lymphocytes, Helper-Inducer; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary | 2008 |
[Immunogenetic aspects of the course and treatment of pulmonary tuberculosis].
The paper presents the clinical, X-ray, and laboratory characteristics of patients with pulmonary tuberculosis. Both general regularities and differences in the frequency of alleles of the HLA-DQB1* locus have been revealed in the groups of patients with pulmonary tuberculosis as compared with healthy individuals. There are specificities associated with the risk of pulmonary tuberculosis and the variants of the course of infection; thus, allele 05 of the HLA-DQB1* locus is positively associated with the incidence of tuberculosis. Specificity 03 of the HLA-DQB1* locus has been ascertained to be associated with the poor course of the disease. The most pronounced immunological changes have been observed in patients with the poor course of the disease, who are the carriers of specificity 05 of the HLA-DQB1* locus. The totality of immunological parameters and the data of genetic studies provide a basis for using the selective immunomodulator rIL-2 (roncoleukin) in the most seriously ill patients who are carriers of specificity 05. Topics: Alleles; Cytokines; HLA-DQ Antigens; HLA-DQ beta-Chains; Humans; Immunologic Factors; Interleukin-2; Interleukin-8; Lymphocytes; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Sensitivity and Specificity; Tuberculosis, Pulmonary | 2008 |
Monocyte-dependent fibroblast CXCL8 secretion occurs in tuberculosis and limits survival of mycobacteria within macrophages.
CXCL8 is a chemokine that is implicated in the formation of tuberculous (TB) granulomas and in immunity to Mycobacterium tuberculosis (Mtb). Fibroblast chemokine secretion is important for modulating inflammatory responses in chronic lung disease and inflammatory arthritis but has not been investigated in the pathophysiology of TB. In this study, we used a cellular model to examine monocyte/macrophage-dependent stimulation of fibroblasts by Mtb in the regulation of chemokine secretion, particularly that of CXCL8. Human lung fibroblasts grown in collagen were stimulated with conditioned medium from Mtb-infected monocytes (CoMTb). CoMTb-induced prolonged dose-dependent, p38-mediated expression of stable CXCL8 mRNA by fibroblasts accompanied by a >10-fold increase in CXCL8 secretion (487 +/- 88 ng/ml vs 48.6 +/- 34 ng/ml in controls) at 120 h. Fibroblasts strongly expressed CXCL8 in vivo in human TB granulomas. Inhibition of TNF-alpha or IL-1 in CoMTb abrogated the induction of CXCL8 at a pretranscriptional level. CXCL8 secretion was NF-kappaB, C/EBP, and JNK dependent. Sustained NF-kappaB activation was demonstrated beyond 24 h in response to CoMTb. Exogenous CXCL8 reduced the survival of Mtb within macrophages, and inhibition of CXCL8 was associated with intracellular mycobacterial proliferation. These data show that fibroblasts have a previously unrecognized role in modulating inflammation in TB by their CXCL8-dependent contribution to cell recruitment and mycobacterial killing within the granuloma. Topics: CCAAT-Enhancer-Binding Proteins; Cells, Cultured; Fibroblasts; Humans; Interleukin-1; Interleukin-8; Macrophages; MAP Kinase Kinase 4; Microbial Viability; Mycobacterium tuberculosis; NF-kappa B; RNA, Messenger; Tuberculoma; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2007 |
Alveolar macrophages from HIV-infected patients with pulmonary tuberculosis retain the capacity to respond to stimulation by lipopolysaccharide.
The functional capacity of alveolar macrophages (AM) in human immunodeficiency virus (HIV)-infected patients with pulmonary tuberculosis (TB) is not completely understood. To investigate the capacity of AM to mediate inflammatory responses, we obtained AM from human subjects by bronchoalveolar lavage (BAL) and studied the cells ex vivo. We compared AM from HIV-infected patients with suspected pulmonary TB to AM from healthy, HIV-negative controls for their capacity to produce TNF-alpha or IL-6 spontaneously and upon stimulation with lipopolysaccharide (LPS). Cytokine-producing cells were identified by macrophage markers and intracellular cytokine staining and flow cytometry. A higher proportion of AM from patients with microbiologically confirmed pulmonary TB than patients with probable TB or controls spontaneously expressed TNF-alpha shortly after isolation (geometric means: 38.5%, 23.7% and 15.8%, respectively), suggesting endogenous cytokine production. The proportions of AM spontaneously expressing TNF-alpha positively correlated with peripheral blood CD4(+) T-lymphocyte counts in patients (partial r=0.60, p=0.003) but not controls. Stimulation with LPS resulted in a significant increase in the proportions of TNF-alpha- and IL-6-positive AM from patients and controls (p<0.01). Bronchoalveolar lavage fluid (BALF) from confirmed TB patients also contained higher concentrations of the inflammatory cytokines predominantly produced by macrophages, IL-6 and IL-8, than controls (geometric mean cytokine concentrations per gram of BALF albumin were 1291 pg/g vs. 115 pg/g, p=0.03 for IL-6 and 4739 pg/g vs. 704 pg/g, p=0.03 for IL-8). We concluded that AM from HIV-infected patients with pulmonary TB produced and released inflammatory cytokines in vivo and retained their innate ability to respond to stimulation by LPS. Topics: Adult; Bronchoalveolar Lavage Fluid; Female; HIV Infections; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharides; Macrophages, Alveolar; Male; Middle Aged; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2007 |
Immune function in young children with previous pulmonary or miliary/meningeal tuberculosis and impact of BCG vaccination.
Children <5 years old are at increased risk of miliary/meningeal tuberculosis, but the immunologic factors that place them at risk are unknown. BCG vaccine protects against miliary/meningeal tuberculosis, but the mechanism of protection is unknown. We assessed for abnormalities in immune response associated with miliary/meningeal or pulmonary tuberculosis in young children.. We conducted a case-control study among HIV-seronegative Brazilian children who were <5 years old. Case subjects had previous culture-confirmed or clinical miliary/meningeal tuberculosis. There were 2 sets of control subjects: those with culture-confirmed pulmonary tuberculosis and purified protein derivative-positive household contacts. All of the children had completed treatment. Peripheral blood mononuclear cells were stimulated (phytohemagglutinin, phytohemagglutinin + interleukin 12, lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative), and cytokine responses (interleukin 1beta, interleukin-4, interleukin-6, interleukin-8, interleukin 10, interleukin 12, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemoattractant protein 1) were quantified by bead-based assay. Median cytokine responses were compared by the Kruskal-Wallis test. Multivariate analysis of variance accounted for multiple comparisons.. There were 18 case subjects with miliary/meningeal tuberculosis, 28 pulmonary control subjects, and 29 purified protein derivative-positive control subjects. The median age was 4.2 years. There was no difference in case and control subjects by age, gender, race, BMI, or median CD4 count. Twelve (67%) of 18 case subjects, 26 (93%) of 28 pulmonary control subjects, and 28 (97%) of 29 purified protein derivative-positive subjects had received BCG vaccine. No cytokine defects were identified in case subjects with miliary/meningeal tuberculosis compared with either set of control subjects. Pulmonary control subjects had uniformly higher monocyte chemoattractant protein 1 levels than case subjects with miliary/meningeal tuberculosis and purified protein derivative-positive control subjects, both at rest and with lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative stimulation. Pulmonary control subjects did not have a higher frequency of allele G in the -2518 monocyte chemoattractant protein 1 promoter polymorphism. Case subjects with miliary/meningeal tuberculosis who had received BCG vaccine (n = 12) had lower stimulated interleukin 8 production than children who did not receive BCG vaccine (n = 6).. Children with previous miliary/meningeal tuberculosis did not have a major defect in the cytokine pathways studied. Increased monocyte chemoattractant protein 1 levels were associated with pulmonary disease, occurred despite BCG vaccination, and were not associated with a polymorphism in the monocyte chemoattractant protein 1 promoter. Topics: BCG Vaccine; Brazil; Case-Control Studies; Chemokine CCL2; Child; Child, Preschool; Female; Gene Frequency; Genotype; Humans; Interferon-gamma; Interleukin-8; Lipopolysaccharides; Lymphocyte Activation; Male; Phytohemagglutinins; T-Lymphocytes; Tuberculin; Tuberculosis, Meningeal; Tuberculosis, Pulmonary | 2007 |
Interleukin-8 polymorphism is not associated with pulmonary tuberculosis in the gambia.
Topics: Alleles; Case-Control Studies; Gambia; Genetic Predisposition to Disease; Humans; Interleukin-8; Mycobacterium tuberculosis; Polymorphism, Genetic; Tuberculosis, Pulmonary | 2004 |
Induction of nitric oxide release from the human alveolar epithelial cell line A549: an in vitro correlate of innate immune response to Mycobacterium tuberculosis.
In view of the presence of a large number of epithelial cells in the alveoli of the lung and their ability to produce various cytokines and chemokines, the possible role of alveolar epithelial cells in the innate immune response to tuberculosis was examined. The human alveolar epithelial cell line A549 was used as a model. The ability of A549 cells to induce nitric oxide (NO) in response to Mycobacterium tuberculosis infection was taken as an in vitro correlate of innate immunity. M. tuberculosis infection induced A549 cells to produce significant levels of NO and to express inducible nitric oxide synthase mRNA at 48 hr of infection. However, the amount of NO released at this point was not mycobactericidal. Cytokine stimulation (interferon-gamma, tumour necrosis factor-alpha, interleukin-1beta, alone or in combination) of the infected A549 cells induced a higher concentration of NO. The study of colony-forming units (CFU) as a measure of the mycobactericidal capacity of A549 cells revealed a reduction in CFU of M. tuberculosis by 39.29% (from 10.62 +/- 0.48 - 6.392 +/- 0.54) following cytokine stimulation of the infected cells. Interestingly gamma-irradiated M. tuberculosis H37Rv could also induce higher than basal level of NO. Therefore we examined mycobacterial antigenic components for their possible role in NO production. We observed that A549 cells produced significantly higher amounts of NO at 48 hr when treated with mycobacterial whole cell lysates, cell wall or cell membrane preparations. The release of NO and the resultant mycobactericidal activity could be further enhanced by simultaneously conditioning the M. tuberculosis infected A549 cells with cytokine and mycobacterial components. These results suggest that alveolar epithelial cells respond to their microenvironment, which is constituted of various cytokines and macrophage-processed antigens and may contribute to the innate immune response to tuberculosis. Topics: Cell Line; Epithelial Cells; Humans; Interferon-gamma; Interleukin-1; Interleukin-8; Mycobacterium tuberculosis; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pulmonary Alveoli; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2004 |
Association between interleukin-8 gene alleles and human susceptibility to tuberculosis disease.
Interleukin (IL)-8 is involved in the pathogenesis of human tuberculosis (TB). However, the contribution of polymorphisms of the IL-8 gene and its receptor genes CXCR-1 and CXCR-2 to human TB susceptibility remains untested. In a case-control study, white subjects with TB disease were more likely to be homozygous for the IL-8 -251A allele, compared with control subjects (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.52-7.64). African Americans with TB also showed an increased odds of being homozygous for this allele (OR, 3.46; 95% CI, 1.48-8.08). To exclude population artifacts in the case-control study, a separate analysis that used a transmission-disequilibrium test with 76 informative families confirmed that the IL-8 -251A allele was preferentially transmitted to TB-infected children (P=.02). CXCR-1 and CXCR-2 did not demonstrate significant associations with TB susceptibility. These data suggest that IL-8 is important in the genetic control of human TB susceptibility. Topics: Adolescent; Alleles; Black People; Case-Control Studies; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Infant; Interleukin-8; Linkage Disequilibrium; Male; Middle Aged; Mycobacterium tuberculosis; Nuclear Family; Texas; Tuberculosis; Tuberculosis, Pulmonary; White People | 2003 |
Changes of plasma interleukin-1 receptor antagonist, interleukin-8 and other serologic markers during chemotherapy in patients with active pulmonary tuberculosis.
The human immune response to Mycobacterium tuberculosis is mediated by macrophages and T-lymphocytes. The alveolar macrophage phagocyting mycobacterium produces interleukin (IL)-1 as an inflammatory mediator, and IL-8 as a cytokine for leukocyte recruitment and granuloma formation. Interleukin-1 receptor antagonist (IL-1ra) is an internal antagonist of IL-1.. Plasma levels of IL-1ra and IL-8 and other serologic markers were measured in 18 patients with active tuberculosis before treatment and after 2 months and 6 months of treatment.. During treatment with antituberculous medication, patients showed significant changes in hemoglobin, hematocrit, white blood cells (WBC), platelet, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin and plasma IL-1ra. After 2 months of treatment, ESR and CRP diminished significantly; after 6 months, hemoglobin increased while WBC, platelet, ESR, CRP and ferritin decreased significantly compared to their pre-treatment levels. There were two groups: patients with delayed therapeutic responses, and patients with early responses. At each point of observation, the former group of patients showed lower body weight and lower levels of hemoglobin and hematocrit, and higher levels of WBC, platelet, ESR, IL-8 and IL-1ra than the latter group. During the course of the treatment, we observed considerable differences in body weight, body mass index, hemoglobin, hematocrit, WBC and platelet counts, ESR, CRP and ferritin in both the early-response and delayed-response groups.. We believe that the plasma concentrations of IL-1ra and IL-8, which showed different peaks during the course of treatment, reflected their different functions and patterns of secretion. Moreover the concentrations did not seem as sensitive as other inflammatory markers to evaluate disease activity during antituberculosis treatment. However, IL-1ra can be considered a marker for disease activity and response to treatment. Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Biomarkers; C-Reactive Protein; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Male; Middle Aged; Receptors, Interleukin-1; Sialoglycoproteins; Tuberculosis, Pulmonary | 2003 |
Mycobacterium bovis BCG vaccination augments interleukin-8 mRNA expression and protein production in guinea pig alveolar macrophages infected with Mycobacterium tuberculosis.
Alveolar macrophages are likely the first cell type to encounter Mycobacterium tuberculosis in a pulmonary infection, resulting in the production of chemokines. In order to evaluate this response, alveolar macrophages harvested from nonvaccinated and Mycobacterium bovis BCG-vaccinated guinea pigs were infected in vitro with live M. tuberculosis H37Ra or H37Rv (multiplicity of infection, 1:1) or cultured with lipopolysaccharide (10 micro g/ml) for 3, 12, and 24 h. Interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was determined by real-time PCR. Culture supernatants were assayed for guinea pig IL-8 protein by using a human IL-8 enzyme-linked immunosorbent assay kit. Alveolar macrophages harvested from BCG-vaccinated guinea pigs produced significantly more mRNA and protein for IL-8 than alveolar macrophages harvested from nonvaccinated guinea pigs at 12 and 24 h poststimulation or postinfection. Infection with attenuated M. tuberculosis (H37Ra) stimulated alveolar macrophages isolated from BCG-vaccinated guinea pigs to produce significantly more IL-8 mRNA than did alveolar macrophages infected with a virulent strain (H37Rv) at 12 and 24 h postinfection. Significant MCP-1 mRNA production was also detected in stimulated or infected alveolar macrophages; however, prior vaccination did not significantly affect levels of MCP-1 mRNA. Alveolar macrophages isolated from BCG-vaccinated guinea pigs produced significantly more IL-8 mRNA and protein when stimulated for 24 h with heat-killed H37Ra, heat-killed H37Rv, and H37Rv cell wall, but not mannose-capped lipoarabinomannan (ManLAM), than did cells stimulated with media alone. These observations indicate that prior vaccination may alter very early events in the M. tuberculosis-infected lung. Topics: Animals; BCG Vaccine; Chemokine CCL2; Disease Models, Animal; Gene Expression; Guinea Pigs; In Vitro Techniques; Interleukin-8; Lipopolysaccharides; Macrophages, Alveolar; Mycobacterium tuberculosis; RNA, Messenger; Tuberculosis, Pulmonary; Virulence | 2002 |
Elevated levels of alpha-defensins in plasma and BAL fluid of patients with active pulmonary tuberculosis.
To investigate the role of neutrophil peptides named alpha-defensins in patients with pulmonary tuberculosis (TB).. Thirty-seven patients with TB and 25 healthy subjects.. Concentrations of alpha-defensins (human neutrophil peptide [HNP]-1, HNP-2, and HNP-3) were measured by radioimmunoassay in plasma and BAL fluid (BALF). Concentrations of alpha-defensins were significantly higher in plasma and BALF of patients with TB than in healthy subjects. In BALF of patients with TB, the concentration of alpha-defensins correlated positively with the levels of interleukin 8, and higher concentrations of alpha-defensins in BALF were also detected in patients with cavitary lesions. There was an inverse relationship between plasma alpha-defensins and FEV(1)/FVC ratio before treatment, and between plasma concentrations of alpha-defensins before treatment and the improvement in percentage of vital capacity after treatment. Plasma alpha-defensin concentrations returned to the normal range after treatment.. Our data suggest that alpha-defensins released from neutrophils may play an important role in the pathogenesis of TB, and that plasma alpha-defensin concentration may be a useful marker of disease severity and deterioration of pulmonary function. Topics: alpha-Defensins; Biomarkers; Bronchoalveolar Lavage Fluid; Female; Humans; Interleukin-8; Male; Middle Aged; Radioimmunoassay; Tuberculosis, Pulmonary; Vital Capacity | 2002 |
Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance.
Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-gamma) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-gamma levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-gamma levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-gamma immunoreactivities in serum followed kinetics in sputum. TNF-alpha, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-gamma, however, TNF-alpha and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy. Topics: Adolescent; Adult; Aged; Biomarkers; Case-Control Studies; Cell Count; Cytokines; Female; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-6; Interleukin-8; Male; Middle Aged; Mycobacterium tuberculosis; Sputum; Treatment Outcome; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 2002 |
Serum levels of vascular endothelial growth factor and cavity formation in active pulmonary tuberculosis.
In active pulmonary tuberculosis, certain cytokines have been postulated to be related to cavity formation, although the detailed mechanism of cavity formation is not yet known.. We examined the relationship between cavity formation in pulmonary tuberculosis and vascular endothelial growth factor (VEGF), which functions as an angiogenesis factor.. Forty-eight patients with active pulmonary tuberculosis were divided into two groups according to cavity formation as evaluated by chest high-resolution computed tomography. We evaluated serum VEGF levels by enzyme immunoassay.. Group A (with cavities) was comprised of 22 patients and group B (without cavities) was comprised of 26 patients. The serum levels of VEGF were significantly higher in group B (58.733 +/- 21.612 pg/ml) than those in normal individuals (8.739 +/- 3.656 pg/ml) and in group A (13.053 +/- 8.670 pg/ml) (Mann-Whitney U test, p = 0.0149 and p = 0.0481, respectively). Serum levels of interleukin-8 and tumor necrosis factor-alpha were not significantly different between the two groups.. These findings suggested that increased serum VEGF levels subdue cavity formation in active pulmonary tuberculosis. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Endothelial Growth Factors; Female; Humans; Interleukin-8; Japan; Lymphokines; Male; Middle Aged; Solitary Pulmonary Nodule; Tomography, X-Ray Computed; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors | 2001 |
Expression of IL-15 in inflammatory pulmonary diseases.
IL-15 is a T(H)1-related cytokine that shares many biologic activities with IL-2. Both cytokines bind a specific alpha subunit, and they share the same beta and gamma common receptor subunits for signal transduction. IL-15 has recently been shown to be upregulated in T cell-mediated inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. However, the role and expression of IL-15 in inflammatory lung disease has not been investigated.. In the present study we have evaluated the expression of IL-15 mRNA and protein in bronchial biopsy specimens obtained from patients with sarcoidosis (n = 8), tuberculosis (n = 7), chronic bronchitis (n = 10), and bronchial asthma (n = 8) and compared its expression with that seen in normal control subjects (n = 11).. In situ hybridization and immunocytochemistry were used to detect the number of cells expressing IL-15 mRNA and protein, respectively, within sections of bronchial tissues from all subject groups. In addition, double immunocytochemistry was used to characterize the cellular source of IL-15.. The number of IL-15(+) cells was significantly higher within tissue from patients with sarcoidosis, tuberculosis, and chronic bronchitis compared with that in asthmatic patients and normal control subjects. Similar results were obtained for IL-15 immunoreactivity by using immunohistochemistry. Furthermore, double immunostaining revealed that neutrophils and macrophages are the major source of IL-15.. These results suggest that the expression of IL-15 may be associated with T(H)1-mediated chronic inflammatory diseases of the lung. Topics: Asthma; Bronchitis; Humans; Immunohistochemistry; Interleukin-15; Interleukin-8; Neutrophils; RNA, Messenger; Sarcoidosis; Th1 Cells; Tuberculosis, Pulmonary | 2001 |
Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis.
Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients. We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001). On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P < 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05). Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressing (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0. 01). IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = -0.73; P < 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes. Topics: Acquired Immunodeficiency Syndrome; Adult; Female; HIV-1; Humans; Interleukin-8; Leukocytes, Mononuclear; Male; RNA, Messenger; Tuberculosis, Pulmonary | 1999 |
Impaired interleukin-8-induced degranulation of polymorphonuclear neutrophils from human immunodeficiency virus type 1-infected individuals.
Degranulation of peripheral blood polymorphonuclear leukocytes (PMNLs) was monitored in human immunodeficiency virus (HIV) type 1 (HIV-1)-infected individuals with or without pulmonary tuberculosis (HIV/TB and HIV groups, respectively) by measuring the release of beta-glucuronidase induced by interleukin-8 (IL-8). This was increased in a dose-dependent manner in the control groups consisting of healthy blood donors and patients with pulmonary tuberculosis. In contrast, PMNLs from the HIV and HIV/TB groups responded reciprocally in the same assay; that is, higher IL-8 input concentrations resulted in the release of less enzyme than lower IL-8 input concentrations. The degranulation response of PMNLs from HIV-1-infected individuals was similarly altered for another agonist, N-formyl-methionyl-leucyl-phenylalanine, suggesting that impairment of the nonoxidative armature of PMNL was a more generalized phenomenon. However, impaired IL-8-induced degranulation was found to be associated with the reduced expression of both IL-8 receptors, A and B, on whole-blood PMNLs from HIV-1-infected patients compared with that on whole-blood PMNLs from healthy persons. The density of IL-8RA, in particular, was most reduced on the surfaces of PMNLs from those patients with the poorest degranulation in response to IL-8. Inefficient agonist-induced degranulation may contribute to the increased susceptibility of HIV-1-infected persons to secondary microbial infections, this being further exacerbated in HIV/TB patients who, in addition, display defects in phagocytosis and oxidative burst. Topics: Adult; Blood Donors; Cell Degranulation; Dose-Response Relationship, Immunologic; Female; Flow Cytometry; Glucuronidase; HIV Infections; HIV-1; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Tuberculosis, Pulmonary | 1999 |
Reduced expression of interleukin-8 receptors A and B on polymorphonuclear neutrophils from persons with human immunodeficiency virus type 1 disease and pulmonary tuberculosis.
The expression of the two human interleukin (IL)-8 receptors, designated IL-8RA (CXCR-1) and IL-8RB (CXCR-2), on the surface of whole blood polymorphonuclear leukocytes (PMNL) was determined by use of receptor-specific monoclonal antibodies and flow cytometry. Sixteen subjects each were included in 4 study groups: healthy blood donors (ND), patients with pulmonary tuberculosis (TB), human immunodeficiency virus type 1-seropositive patients (HIV), and HIV-1-seropositive subjects with pulmonary tuberculosis (HIV/TB). A significant reduction in the percentage of PMNL expressing IL-8RA and IL-8RB and in their respective fluorescence intensities was found in TB, HIV, and HIV/TB groups compared with that obtained for the ND group. The greatest down-regulation of both receptors occurred in the HIV/TB group. Furthermore, associated with this reduced expression of IL-8 receptors was impairment of both intracellular calcium flux and migration of PMNL in response to IL-8 in a group of HIV/TB patients compared with that in healthy persons. Topics: Adult; AIDS-Related Opportunistic Infections; Antibodies, Monoclonal; Antigens, CD; Antitubercular Agents; Calcium; CD4 Lymphocyte Count; Chemotaxis, Leukocyte; Female; Flow Cytometry; HIV-1; Humans; Interleukin-8; Lymphocytes; Male; Neutrophils; Receptors, Chemokine; Receptors, Interleukin; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Tuberculosis, Pulmonary | 1998 |
Levels of interleukin-8 in tuberculous pleurisy and the profile of immunocompetent cells in pleural and peripheral compartments.
Our study investigated the presence of IL-8 in pleural exudates from tuberculosis patients (TBP) (n = 13), and evaluated whether it was related with the profile of major immunocompetent cells present in their pleural and peripheral compartments. To allow comparisons, an additional group of patients with parapneumonic pleural effusions (PNE) (n = 7) was included. Blood peripheral immunophenotypic studies were also carried out in 12 age-matched healthy controls (Co), and 39 tuberculosis patients classified, according to the extent of pulmonary involvement, into mild (n = 9), and advanced (n = 30) cases. Patients were recruited before starting therapy, had HIV negative serology, and showed no age differences among groups (mean +/- SD., 40.7 +/- 14.7 years). IL-8 concentrations were measured by an ELISA method while immunophenotypic analysis was performed by using FITC-conjugated monoclonal antibodies reacting against the following cell surface molecules: CD3, CD4, CD8, CD25 (IL-2R+ cells), CD19, and CD68. IL-8 was detected in all pleural exudates though levels in the TB patients, 384 +/- 110 pg/ml, appeared significantly higher than the PNE group, 185 +/- 110 pg/mg, (P < 0.015, mean +/- S.D.). In turn, the former group presented values of pleural CD3+, CD4+, and CD25, which were found increased in comparison with PNE patients (P < 0.01). Unlike the pleural compartment, patients with TBP showed a marked and significant decrease in their circulating levels of cells bearing the CD3, CD4, CD19, CD25, and CD68 phenotypes not only when comparing with Co but also with PNE and mild patients. Differences between the levels of pleural and peripheral T-cells from TBP patients may be the reflection of an important influx of T-lymphocytes from the circulatory system to the pleural cavity, probably linked to the presence of chemotactic factors within the pleural fluid like IL-8. Topics: Adolescent; Adult; Aged; Chemotaxis, Leukocyte; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunocompetence; Immunophenotyping; Interleukin-8; Lymphocyte Count; Lymphocyte Subsets; Male; Middle Aged; Pleural Effusion; Pneumonia; Tuberculosis, Pleural; Tuberculosis, Pulmonary | 1997 |
Tuberculosis in HIV-positive patients: cellular response and immune activation in the lung.
The host response to Mycobacterium tuberculosis is dependent on the accumulation and activation of cytotoxic and memory CD4+ T cells, resulting in granuloma formation and delayed type hypersensitivity. We characterized the cellular response of radiographically involved lung segments from 17 HIV-positive and 11 HIV-negative patients with acute tuberculosis (TB) using bronchoalveolar lavage (BAL) and compared the response to uninvolved segments, normal control subjects and peripheral blood. In both HIV-positive and HIV-negative patients, radiographically involved segments had significantly increased numbers of total cells per milliliter, percent of neutrophils recovered, and percent of lymphocytes recovered compared with uninvolved segments or normal control subjects, but HIV-positive patients had a lower proportion of lymphocytes in the involved segments than HIV-negative patients with tuberculosis (19 +/- 5% versus 33 +/- 5%; p < 0.05). Lymphocyte subset analysis demonstrated that HIV-positive patients had markedly reduced percentages of CD4+ lymphocytes (CD4+ lymphocytes in HIV-positive TB involved site 25 +/- 6%; HIV-negative TB involved site 73 +/- 2%; p < 0.01) and an increase in the percentage of CD8+ lymphocytes (HIV positive involved site 61 +/- 6% versus HIV negative involved site 19 +/- 3%; p < 0.01). Immunohistochemistry of lung biopsy tissue in five HIV-negative patients showed similar lymphocyte subset profiles as BAL, indicating that BAL reflects cell populations in tissue granulomas. BAL lymphocytes from four HIV-positive and four HIV-negative tuberculosis patients demonstrated immune activation by staining with a murine antibody to TIA-1, a cytoplasmic protein associated with cytotoxicity and apoptosis (HIV positive 48 +/- 6%, HIV negative 31 +/- 7%, normals 11 +/- 5%). Steady state mRNA for gamma-interferon was decreased in four HIV-positive patients when compared with four HIV-negative patients. IL-8 production was comparable in HIV-negative and HIV-positive patients with focal disease but reduced in two patients with miliary tuberculosis. We conclude that HIV-positive patients with+ tuberculosis have a reduced enrichment and activation of immune cells in the lung, and this failure of a CD4+ alveolitis limits an effective immune response. Topics: Base Sequence; Bronchoalveolar Lavage Fluid; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Immunity, Cellular; Immunohistochemistry; Interferon-gamma; Interleukin-8; Lymphocyte Subsets; Male; Molecular Sequence Data; RNA, Messenger; Tuberculosis, Pulmonary | 1996 |
[The evaluation of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) level in peripheral blood of patients with active pulmonary tuberculosis].
We investigated the serum level of IL-8 and TNF-alpha using ELISA in 16 patients with active pulmonary tuberculosis before administration of antituberculous drugs and in age-, smoking habit-matched 20 healthy controls. The mean level of serum IL-8 in patients with active pulmonary tuberculosis was significantly higher than that in healthy controls (P < 0.001). The mean level of serum TNF-alpha in tuberculosis patients was also high, while TNF-alpha was not detectable in the sera of healthy controls. We also examined the relationship between clinical pictures mainly defined by radiographic findings and the serum levels of IL-8 and TNF-alpha. The serum IL-8 level of 9 patients with tuberculous cavity is significantly higher than that of 7 patients without cavity. (P < 0.05) We classified the patients with cavities into two subgroups according to the radiographic classification of the Japanese Society of Tuberculosis. Four patients with advanced lesions on chest X-ray showed higher serum IL-8 level than 5 patients with moderate lesions (P < 0.05). On the other hand, there was no correlation between serum TNF-alpha level and radiographic findings. These results suggest that IL-8 appears to be involved in the formation of tuberculous cavitary lesion. Topics: Adult; Aged; Female; Humans; Interleukin-8; Male; Middle Aged; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha | 1995 |
Enhanced interleukin-8 release and gene expression in macrophages after exposure to Mycobacterium tuberculosis and its components.
Mycobacterium tuberculosis infection is accompanied by acute and chronic inflammatory infiltrates associated with necrotizing granulomas in lung tissue. The cellular infiltrate is characterized by inflammatory cells which include neutrophils, lymphocytes, and macrophages. In animal and in vitro models of mycobacterial infection, cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) participate in granulomatous inflammation. We hypothesized that interleukin-3, a potent chemoattractant for neutrophils and lymphocytes, could be released by activated alveolar macrophages after exposure to M. tuberculosis or its components and contribute to granulomatous lung inflammation. A quantitative immunoassay revealed that IL-8 protein release was significantly elevated in supernatants of macrophages and in lavage fluid obtained from patients with pulmonary tuberculosis compared to normal controls. In addition, Northern blots demonstrated striking up-regulation of IL-8 mRNA in macrophages from these patients. M. tuberculosis and its cell wall components lipoarabinomannan (LAM), lipomannan (LM), and phosphoinositolmannoside (PIM) stimulated IL-8 protein release and mRNA expression in vitro from alveolar macrophages, but deacylated LAM did not. Neutralizing antibodies to TNF-alpha and/or IL-1-alpha and beta blocked 83% of the stimulation. IL-8 synthesis and release is an early response of macrophages after phagocytosis of M. tuberculosis. Its production serves to attract both acute and chronic inflammatory cells of active infection and thus participates in the process of containment of the pathogen. Topics: Adult; Animals; Antigens, Bacterial; Blotting, Northern; Bronchoalveolar Lavage Fluid; Cell Wall; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Humans; Interleukin-8; Lipopolysaccharides; Macrophage Activation; Macrophages, Peritoneal; Male; Monocytes; Mycobacterium tuberculosis; Phosphatidylinositols; Reference Values; RNA, Messenger; Tuberculosis, Pulmonary | 1995 |
Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression.
Phagocytosis of Mycobacterium tuberculosis by human monocytes or macrophages is classically followed by granuloma formation in vivo. Granuloma are comprised of cells of the monocyte lineage together, in many instances, with antigen-specific T lymphocytes. Development of granuloma depends upon recruitment of both cell types, but recruitment of monocytes is pivotal as these cells secrete anti-mycobacterial cytokines and IL-8, a T cell chemoattractant. We have therefore investigated gene regulation of Monocyte Chemotactic Protein 1 (MCP-1), an important monocyte chemotactic cytokine, following phagocytosis of particulate material (latex beads and zymosan) and live M. tuberculosis by two human monocytic cell lines. In THP-1 cells and phenotypically more differentiated Mono Mac 6 cells, MCP-1 mRNA accumulation was first detectable by Northern analysis of 4 hours and increased over 24 hours. Magnitude and kinetics of MCP-1 gene expression was independent of the biochemical nature of the phagocytic stimulus, M. tuberculosis strain virulence or pre-treatment with anti-TNF. In contrast to the uniform effect of different phagocytic stimuli on MCP-1 gene expression, we have shown that M. tuberculosis but not latex or zymosan, increased IL-8 gene expression, a chemotactic agent for T cells. In additional experiments with THP-1 cells infected with human immunodeficiency virus (HIV), viral infection did not alter MCP-1 gene expression following phagocytosis. MCP-1 gene expression appears to be a conserved antigen-independent response of human monocytic cells which is activated following particulate phagocytosis. MCP-1 gene expression may thus be involved in recruitment of monocytes during granuloma formation.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Cell Line; Chemokine CCL2; Chemotactic Factors; Cycloheximide; Dactinomycin; Gene Expression Regulation; HIV Infections; Humans; Interleukin-8; Monocytes; Mycobacterium tuberculosis; Phagocytosis; RNA; Tuberculosis, Pulmonary | 1993 |
Recruitment of inflammatory cells to the pleural space. Chemotactic cytokines, IL-8, and monocyte chemotactic peptide-1 in human pleural fluids.
Pleural effusions secondary to various diseases are associated with the presence of different inflammatory cells. The role of selective chemotactic cytokines in the recruitment of phagocytes to the pleural space is unclear. IL-8 and monocyte chemotactic peptide-1 (MCP-1) are recently described cytokines that are chemotactic for neutrophils and monocytes, respectively. We prospectively studied 63 patients, using strictly defined criteria for their selection. IL-8 concentrations were elevated in both empyema fluid (9.15 +/- 0.89 ng/ml) and parapneumonic effusions (4.7 +/- 0.697 ng/ml) when compared with pleural effusions secondary to other diseases. IL-8 levels were higher in empyema fluid than in parapneumonic effusions (p = 0.01). There was a significant correlation between IL-8 levels and the total numbers of neutrophils in empyema fluids (r = 0.80). Chemotactic activity for neutrophils was elevated in empyema fluid and the addition of IL-8 neutralizing serum decreased bioactivity by 32.22%. Malignant pleural effusions had the highest levels of MCP-1 (12.0 +/- 3.7 ng/ml) when compared with others. Cytology-positive pleural fluids (n = 10) had a higher level of MCP-1 than cytology-negative effusions (p = < 0.05). Malignant pleural fluid MCP-1 levels correlated (r = 0.70) with the absolute number of monocytes in the pleural fluid. Neutralization of monocyte chemotactic activity of malignant pleural fluid by specific neutralizing serum caused a 70.3% inhibition of bioactivity. Immunohistochemical staining of malignant pleural fluid localized antigenic MCP-1 to malignant cells. We conclude that both IL-8 and MCP-1 play major but not exclusive roles in the recruitment of neutrophils and monocytes from the vascular compartment to the pleural space. Topics: Chemokine CCL2; Chemotactic Factors; Cytokines; Empyema; Heart Failure; Humans; Immunohistochemistry; Interleukin-8; Pleural Effusion; Pleural Effusion, Malignant; Pleurisy; Pneumonia; Tuberculosis, Pulmonary | 1993 |