Value of serum cytokine biomarkers TNF-α, IL-4, sIL-2R and IFN-γ for use in monitoring bacterial load and anti-tuberculosis treatment progress

Nie, Wenjuan; Wang, Jun; Wei, Jing; Shi, Wenhui; Wang, Qingfeng; Huang, Xue-rui; Cai, Baoyun; Ge, Qiping; Nie, Lihui; Han, Xu; Du, Yadong; Wang, Jing; Guo, Runmin; Chu, Naihui

doi:10.1016/j.cytox.2020.100028

Cited by 14 publications

(7 citation statements)

References 44 publications

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“…To reflect the inflammatory levels during TB treatment, we examined the expression levels of several related cytokines and chemokines including CXCL10, CCL2, IL-6, IL-8, IL-1β, TNF-α, and IFN-γ ( 18 – 21 ) by flow cytometry analysis using the plasma samples from our cohort. The expression profiles of plasma cytokines were shown in Figure 2A , and the levels of cytokines were showed in Figure 2B .…”

Section: Resultsmentioning

confidence: 99%

Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients

Qiao

Yuan

et al. 2022

Front. Immunol.

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BackgroundApart from bactericidal effects, anti-tuberculosis drugs can interfere with the host’s immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages.MethodsBased on a cohort of multidrug-resistant tuberculosis (MDR-TB) patients treated with DLM, the levels of C-reaction protein (CRP) and cytokines in the plasma were monitored using immunoturbidimetric assay and flow cytometry, respectively. We investigated the role of DLM on CXCL10 expression in U937 cell model using the following methods: cell viability assay, reverse transcription-quantitative polymerase chain reaction, enzyme linked immunosorbent assay, immunoblot, and transwell co-culture assay.ResultsA total of 23 MDR-TB patients were included, comprising of 13 patients treated with optimized background therapeutic regimen (OBR) plus DLM regimen (OBR+DLM) and 10 patients treated with OBR plus placebo. DLM administration was associated with a significant reduce in circulating CRP level. Correspondingly, after treatment, the level of CXCL10 in patients treated with OBR+DLM was significantly lower than that with control. Using cell model, DLM dramatically suppressed CXCL10 expression, which majorly depended on inhibiting the JAK/STAT pathway, and impaired the migration of PBMCs.ConclusionOur data firstly demonstrate that DLM suppresses CXCL10 expression via regulation of JAK2/STAT1 signaling and correlates with reduced inflammation in MDR-TB patients. DLM could be used as a potential drug for immunotherapy of patients with overactive immune response due to CXCL10.

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Section: Resultsmentioning

confidence: 99%

Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients

Qiao

Yuan

et al. 2022

Front. Immunol.

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“…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%

“…Inflammatory cytokines (e.g., IL‐6, TNF‐α and IFN‐γ) were shown to be associated with disease severity and/or higher mycobacterial burden [20, 37, 43, 59, 73, 74]. In accordance, several studies detected decreasing plasma levels of inflammatory cytokines during treatment [20, 21, 37, 44, 59, 68, 73, 75–77]. Such markers may also provide clinically relevant information as some were described to predict treatment outcomes [78–83] and others may indicate the risk of recurrent tuberculosis [70, 84, 85].…”

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

confidence: 96%

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

Ahor,

Vivekanandan,

Harelimana

et al. 2024

Immunology

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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.

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“…A similar finding was reported by Hussain et al, who observed higher levels of IFN-γ among TB patients confirmed by ZN staining and histopathological findings as compared to clinically diagnosed cases 30 . Though there are conflicting reports about the correlation of IFN-γ with bacillary load in TB, various studies have reported a progressive decrease in the levels of IFN-γ with treatment; hence, IFN-γ might prove useful in monitoring the efficacy of antitubercular therapy 31 .…”

Section: Gupta N Et Al Il-12 and Ifn-γ In Pediatric Tbmentioning

confidence: 99%

Serum Levels of Interleukin-12 and Interferon Gamma in Pediatric Tuberculosis: A Clinico-Microbiological Correlation

Gupta¹,

Kashyap

Dewan

et al. 2023

J Health Sci Med Res

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Objective: The interleukin-12/interferon-γ (IL-12/IFN-γ) pathway is the most validated cytokine pathway regulating Mycobacterium tuberculosis infection. The role of IL-12/IFN-γ axis in protecting against tuberculosis (TB) is exhibited in people having mutations in genes encoding these cytokines. We aimed to study the serum levels of IL-12 and IFN-γ in pediatric tuberculosis and their correlation with clinical and microbiological features. Material and Methods: A case-control study was conducted on 60 microbiologically confirmed (smear and/or culture and/or cartridge-based nucleic acid amplification test) or clinically diagnosed (based on clinical features and radiography and/or contact history and/or Mantoux test with/without microbiological confirmation) pediatric TB patients ≤12 years. Serum interleukin-12 and interferon-gamma levels were estimated using enzyme-linked immunosorbent assays.Thirty age- and sex-matched controls were also included in the study. Results: The median IL-12 levels were lower in our pediatric TB patients (488.1 pg/ml) compared to controls (784.8 pg/ml). However, the IFN-γ/IL-12 ratios were significantly higher among the TB patients as compared to the controls. Moreover, the levels of interleukin-12 and interferon gamma were significantly lower in cases with no evidence of TB on chest radiography. IL-12 was significantly lower in patients with hydrocephalus and enlarged ventricles. Higher levels of IL-12 and IFN-γ were associated with positive results by conventional microbiological techniques. Conclusion: The serum IFN-γ level and the IFN-γ/IL-12 ratio were significantly higher in children with TB compared to the controls in this study. Higher IL-12 and IFN-γ levels as well as IFN-γ/IL-12 ratios were associated with positive results by conventional microbiological techniques. Further studies on larger sample sizes could help evaluate the usefulness of interleukin-12 and interferon-γ as potential markers of severity and prognosis in pediatric TB.

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Value of serum cytokine biomarkers TNF-α, IL-4, sIL-2R and IFN-γ for use in monitoring bacterial load and anti-tuberculosis treatment progress

Cited by 14 publications

References 44 publications

Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients

Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients

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

Serum Levels of Interleukin-12 and Interferon Gamma in Pediatric Tuberculosis: A Clinico-Microbiological Correlation

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