Association of plasma cytokines with radiological recovery in pulmonary tuberculosis patients

Iqbal, Najeeha Talat; Hussain, Rabia; Shahid, Firdaus; Dawood, Ghaffar

doi:10.1016/j.ijmyco.2015.12.003

Cited by 6 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study suggested CXCR3 ligands (CXCL9 and CXCL10) as useful surrogate markers in plasma for diagnosing active TB clinically (Lee et al, 2015a). More recently, when plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were determined during the follow-up of anti-TB chemotherapy, slow responders showed significantly higher IL-2 and IL-4 levels at baseline than did fast responders, effectively differentiating the two responder types (Iqbal et al, 2016). Considering these reports, a systematic analysis of immune response genes is essential to understand diverse immune reactions in tuberculosis.…”

Section: Discussionmentioning

confidence: 99%

Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model

Park

Baek

Cho

et al. 2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

There is a substantial need for biomarkers to distinguish latent stage from active Mycobacterium tuberculosis infections, for predicting disease progression. To induce the reactivation of tuberculosis, we present a new experimental animal model modified based on the previous model established by our group. In the new model, the reactivation of tuberculosis is induced without administration of immunosuppressive agents, which might disturb immune responses. To identify the immunological status of the persistent and chronic stages, we analyzed immunological genes in lung tissues from mice infected with M. tuberculosis. Gene expression was screened using cDNA microarray analysis and confirmed by quantitative RT-PCR. Based on the cDNA microarray results, 11 candidate cytokines genes, which were obviously up-regulated during the chronic stage compared with those during the persistent stage, were selected and clustered into three groups: (1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs; CXCL9, CXCL10, CXCL11, CCL5, CCL19); (2) MCP genes (CCL2, CCL7, CCL8, CCL12); and (3) TNF and IFN-γ genes. Results from the cDNA microarray and quantitative RT-PCR analyses revealed that the mRNA expression of the selected cytokine genes was significantly higher in lung tissues of the chronic stage than of the persistent stage. Three chemokines (CCL5, CCL19, and CXCL9) and three MCPs (CCL7, CCL2, and CCL12) were noticeably increased in the chronic stage compared with the persistent stage by cDNA microarray (p < 0.01, except CCL12) or RT-PCR (p < 0.01). Therefore, these six significantly increased cytokines in lung tissue from the mouse tuberculosis model might be candidates for biomarkers to distinguish the two disease stages. This information can be combined with already reported potential biomarkers to construct a network of more efficient tuberculosis markers.

show abstract

Section: Discussionmentioning

confidence: 99%

Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model

Park

Baek

Cho

et al. 2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Only a few cytokines show an unambiguous picture of being either higher or lower in tuberculosis patients' plasma. Particularly, frequently studied candidate cytokines, such as TNF‐α or IFN‐γ, were elevated in the plasma of tuberculosis patients in several studies [20, 23–26, 29, 30, 32, 37, 44, 45, 47, 57, 60, 62, 68–71], but either or both did not differ in other studies [7–10, 14, 15, 18, 20, 21, 23–26, 29–32, 37, 40, 42, 44–47, 51–54, 57, 60–64, 68–71] (Figure 1b). Insufficient study cohort sizes and low statistical power in some studies likely contribute to heterogeneity, but this does not sufficiently explain differences.…”

Section: Heterogeneity Of Plasma Cytokine Expression In Pulmonary Tub...mentioning

confidence: 93%

“…However, to provide an overview of candidates, we screened studies based on a case/control design comparing ‘plasma’ or ‘serum’ samples from patients with pulmonary tuberculosis (before treatment) and matched controls. Sixty studies were identified that meet these criteria [7–66]. The selection criteria used for the definition of ‘controls’ varied between the studies, and this is at least partially due to a missing gold standard for the classification of ‘controls’ in human tuberculosis.…”

Section: Aberrant Plasma Cytokines In Tuberculosis Patients Reflect P...mentioning

confidence: 99%

Immunopathology in human pulmonary tuberculosis: Inflammatory changes in the plasma milieu and impaired host immune cell functions

Ahor,

Vivekanandan,

Harelimana

et al. 2024

Immunology

View full text Add to dashboard Cite

Host immune response is key for protection in tuberculosis, but the causative agent, Mycobacterium (M.) tuberculosis, manages to survive despite immune surveillance. Key mechanisms of immune protection have been identified, but the role of immunopathology in the peripheral blood of tuberculosis patients remains unclear. Tuberculosis immunopathology in the blood is characterised by patterns of immunosuppression and hyperinflammation. These seemingly contradictory findings and the pronounced heterogeneity made it difficult to interpret the results from previous studies and to derive implications of immunopathology. However, novel approaches based on comprehensive data analyses and revitalisation of an ancient plasma milieu in vitro assay connected inflammation with immunosuppressive factors in tuberculosis. Moreover, interrelations between the aberrant plasma milieu and immune cell pathology were observed. This review provides an overview of studies on changes in plasma milieu and discusses recent findings linking plasma factors to T‐cell and monocyte/macrophage pathology in pulmonary tuberculosis patients.

show abstract

Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy

et al. 2018

View full text Add to dashboard Cite

BackgroundWe have previously shown that 8 weeks’ treatment with phenylbutyrate (PBA) (500mgx2/day) with or without vitamin D3 (vitD3) (5000 IU/day) as host-directed therapy (HDT) accelerated clinical recovery, sputum culture conversion and increased expression of cathelicidin LL-37 by immune cells in a randomized, placebo-controlled trial in adults with pulmonary tuberculosis (TB). In this study we further aimed to examine whether HDT with PBA and vitD3 promoted clinically beneficial immunomodulation to improve treatment outcomes in TB patients.MethodsCytokine concentration was measured in supernatants of peripheral blood mononuclear cells (PBMC) from patients (n = 31/group). Endoplasmic reticulum stress-related genes (GADD34 and XBP1spl) and human beta-defensin-1 (HBD1) gene expression were studied in monocyte-derived-macrophages (MDM) (n = 18/group) from PBMC of patients. Autophagy in MDM (n = 6/group) was evaluated using LC3 expression by confocal microscopy.ResultsA significant decline in the concentration of cytokines/chemokines was noted from week 0 to 8 in the PBA-group [TNF-α (β = − 0.34, 95% CI = − 0.68, − 0.003; p = 0.04), CCL11 (β = − 0.19, 95% CI = − 0.36, − 0.03; p = 0.02) and CCL5 (β = − 0.08, 95% CI = − 0.16, 0.002; p = 0.05)] and vitD3-group [(CCL11 (β = − 0.17, 95% CI = − 0.34, − 0.001; p = 0.04), CXCL10 (β = − 0.38, 95% CI = − 0.77, 0.003; p = 0.05) and PDGF-β (β = − 0.16, 95% CI = − 0.31, 0.002; p = 0.05)] compared to placebo. Both PBA- and vitD3-groups showed a decline in XBP1spl mRNA on week 8 (p < 0.03). All treatment groups demonstrated increased LC3 expression in MDM compared to placebo over time (p < 0.037).ConclusionThe use of PBA and vitD3 as adjunct therapy to standard TB treatment promoted favorable immunomodulation to improve treatment outcomes.Trials registrationThis trial was retrospectively registered in clinicaltrials.gov, under identifier NCT01580007.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3203-9) contains supplementary material, which is available to authorized users.

show abstract

Association of plasma cytokines with radiological recovery in pulmonary tuberculosis patients

Abstract: In-depth analysis of cytokines and its association with radiological recovery in TB patients may be useful in monitoring TB patients postchemotherapy for both clinicians and TB control program.

Cited by 6 publications

References 25 publications

Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model

Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model

Immunopathology in human pulmonary tuberculosis: Inflammatory changes in the plasma milieu and impaired host immune cell functions

Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy

Contact Info

Product

Resources

About