Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Patient Selection and Group Allocation
2.3. Data Collection and Variable Definitions
2.4. Laboratory Procedures
2.5. Statistical Analysis
3. Results
Patient Demographics
4. Discussion
4.1. Analysis of Findings
4.2. Study Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADA | Adenosinedeaminase |
ACE | Angiotensin-convertingenzyme |
AUROC | Area under the receiver-operating-characteristic curve |
BCG | Bacille Calmette–Guérin(vaccine) |
BMI | Body mass index |
COPD | Chronicobstructive pulmonary disease |
COVID-19 | Coronavirus disease 2019 |
CRP | C-reactive protein |
CT | Computed tomography |
CXCL | C-X-C motif chemokine ligand |
ECDC | European Centres for Disease Prevention and Control |
EPTB | Extrapulmonary tuberculosis |
EU | European Union |
GBD | Global Burden of Disease study |
HDT | Host-directed therapy |
HIV | Human immunodeficiency virus |
ICH | International Conference on Harmonisation |
IFN-γ | Interferon-gamma |
IL-1α | Interleukin-1-alpha |
IL-1β | Interleukin-1-beta |
IL-6 | Interleukin-6 |
IL-10 | Interleukin-10 |
IRB | Institutional review board |
IRR | Incidence-rate ratio |
IQR | Inter-quartile range |
LOS | Length of stay |
MDR-TB | Multidrug-resistant tuberculosis |
MGIT | Mycobacteria Growth Indicator Tube (culture system) |
miR | Micro-RNA |
MMP-9 | Matrixmetalloproteinase-9 |
NLR | Neutrophil-to-lymphocyte rratio |
NTP | (Romanian) National Tuberculosis Control Programme |
OR | Odds ratio |
PBMC | Peripheral-blood mononuclear cell |
pSWE | Point shear-wave elastography |
ROC | Receiver-operating-characteristic curve |
R2 | Coefficient of determination |
SD | Standard deviation |
STROBE | Strengthening the Reporting of Observational Studies in Epidemiology |
TB | Tuberculosis |
Th1 | Type-1 helper T-cell response |
TNF-α | Tumour-necrosis-factor-alpha |
WHO | World Health Organization |
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Variable | TB (n = 80) | Controls (n = 40) | p-Value |
---|---|---|---|
Age, years (mean ± SD) | 50.1 ± 14.8 | 46.6 ± 8.4 | 0.096 |
Male sex, n (%) | 63 (78.8) | 15 (37.5) | <0.001 |
Variable | n (%) |
---|---|
Current smoker | 59 (76.6) |
Chronic alcohol use | 23 (29.9) |
Occasional alcohol use | 5 (6.5) |
Known household TB contact | 13 (16.9) |
≥1 prior COVID-19 episode | 24 (31.2) |
Currently employed | 35 (45.5) |
Symptomatic at presentation | 77 (96.3) |
Symptom duration | |
<4 weeks | 33 (41.3) |
4–12 weeks | 23 (28.7) |
>12 weeks | 21 (26.2) |
BMI category | |
Underweight (<18.5 kg·m−2) | 22 (27.5) |
Normal (18.5–24.9) | 47 (58.7) |
Overweight (≥25) | 11 (13.8) |
≥1 comorbidity | 25 (31.2) |
Single comorbidity | 17 (21.2) |
≥2 comorbidities | 8 (10.0) |
Median length of stay, days (IQR) | 29 (23–34) |
Marker | TB Median (IQR) pg/mL | Control Median (IQR) pg/mL | p |
---|---|---|---|
IFN-γ | 4.84 (3.11–8.41) | 4.14 (2.31–12.87) | 0.527 |
IL-1α | 3.57 (1.62–9.19) | 4.12 (0.68–16.40) | 0.599 |
IL-1β | 5.34 (3.93–16.35) | 3.67 (2.48–8.31) | 0.008 |
TNF-α | 24.11 (18.42–43.15) | 16.21 (8.02–43.15) | 0.009 |
NLR | 4.01 (2.44–7.28) | 2.78 (1.93–4.05) | 0.071 |
Marker | Survivors (n = 76) Median (IQR) | Non-Survivors (n = 4) Median (IQR) | p |
---|---|---|---|
IFN-γ | 4.84 (3.02–8.32) | 8.66 (4.67–19.26) | 0.22 |
IL-1α | 3.57 (1.62–8.37) | 9.09 (1.89–26.41) | 0.74 |
IL-1β | 3.56 (2.43–8.13) | 18.07 (4.94–46.03) | 0.079 |
TNF-α | 23.20 (18.19–37.54) | 71.43 (48.69–140.22) | 0.037 |
NLR | 3.70 (1.95–5.55) | 7.84 (2.55–9.41) | 0.002 |
Variables | IFN-γ | IL-1α | IL-1β | TNF-α | NLR |
---|---|---|---|---|---|
IFN-γ | 1 | ρ = 0.57 * | 0.68 * | 0.66 * | 0.05 |
IL-1α | 0.57 * | 1 | 0.68 * | 0.67 * | 0.08 |
IL-1β | 0.68 * | 0.68 * | 1 | 0.80 * | 0.19 |
TNF-α | 0.66 * | 0.67 * | 0.80 * | 1 | 0.16 |
NLR | 0.05 | 0.08 | 0.19 | 0.16 | 1 |
Subgroup | n | Median LOS (Days) | Comparator n | Median LOS | p |
---|---|---|---|---|---|
Smoking vs. non-smoking | 59 | 28 | 18 | 31 | 0.41 |
≥1 comorbidity vs. none | 25 | 28 | 52 | 29 | 0.69 |
BMI categories | 0.03 † | ||||
Underweight | 22 | 27 | — | — | |
Normal | 47 | 30 | — | — | |
Overweight | 8 | 23 | — | — |
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Stanciu, I.-V.; Fildan, A.-P.; Ilie, A.C.; Oancea, C.; Stanga, L.; Tudorache, E.; Bratosin, F.; Rosca, O.; Bogdan, I.; Tofolean, D.-E.; et al. Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis. J. Clin. Med. 2025, 14, 5327. https://doi.org/10.3390/jcm14155327
Stanciu I-V, Fildan A-P, Ilie AC, Oancea C, Stanga L, Tudorache E, Bratosin F, Rosca O, Bogdan I, Tofolean D-E, et al. Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis. Journal of Clinical Medicine. 2025; 14(15):5327. https://doi.org/10.3390/jcm14155327
Chicago/Turabian StyleStanciu, Ionut-Valentin, Ariadna-Petronela Fildan, Adrian Cosmin Ilie, Cristian Oancea, Livia Stanga, Emanuela Tudorache, Felix Bratosin, Ovidiu Rosca, Iulia Bogdan, Doina-Ecaterina Tofolean, and et al. 2025. "Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis" Journal of Clinical Medicine 14, no. 15: 5327. https://doi.org/10.3390/jcm14155327
APA StyleStanciu, I.-V., Fildan, A.-P., Ilie, A. C., Oancea, C., Stanga, L., Tudorache, E., Bratosin, F., Rosca, O., Bogdan, I., Tofolean, D.-E., Preotesoiu, I., Zamfir, V., & Dantes, E. (2025). Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis. Journal of Clinical Medicine, 14(15), 5327. https://doi.org/10.3390/jcm14155327