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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 3  |  Page : 1104-1107

Correlation between serum tumor necrosis factor-α levels and clinicoradiological severity of tuberculosis


1 Department of Chest, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Chest, El-Mansoura Chest Hospital, El-Mansoura, Dakahlia, Egypt

Date of Submission26-Nov-2017
Date of Acceptance09-Jan-2018
Date of Web Publication17-Oct-2019

Correspondence Address:
Fatma S El-Fakharany
El-Galaa, Mansoura, Dakahlia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_830_17

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  Abstract 

Objective
The aim was to assess the level of tumor necrosis factor-α (TNF-α) in patients with active pulmonary tuberculosis (TB) and its relation to BMI; different radiological features whether the lesion is minimally, moderately advanced, and far advanced; and to follow-up the level of TNF-α.
Background
One of the most important and common complaints of patients with TB, which also affects the immune status, is weight loss. When tuberculous infection occurs, a variety of chemokines and cytokines are secreted from infected cells and tissue macrophages. TNF-α increases early in the disease and takes part in the pathogenesis and prevention of mycobacterial infection.
Participants and methods
Serum TNF-α was measured in 40 newly diagnosed patients as having active pulmonary TB (group I) and 10 controls (group II).
Results
Serum TNF-α level was significantly higher in patients with active pulmonary TB than in controls, and there was a highly significant negative correlation between TNF-α level and BMI before and after treatment. Serum TNF-α had insignificant positive correlation with grades of Ziehl–Neelsen stain and chest radiography before and after treatment, and the diagnostic cut-off points of TNF-α was found to be 618.1 pg/ml.
Conclusion
Serum TNF-α level is higher in patients with TB than in controls. TNF-α plays a role in diminishing appetite, in weight loss, and in increased susceptibility to infection.

Keywords: active tuberculosis, chest radiography, loss of weight, tumor necrosis factor-α, Ziehl–Neelsen stain


How to cite this article:
Ali AA, El-Mahalawy II, El-Dahdouh SS, Habib MS, El-Fakharany FS. Correlation between serum tumor necrosis factor-α levels and clinicoradiological severity of tuberculosis. Menoufia Med J 2019;32:1104-7

How to cite this URL:
Ali AA, El-Mahalawy II, El-Dahdouh SS, Habib MS, El-Fakharany FS. Correlation between serum tumor necrosis factor-α levels and clinicoradiological severity of tuberculosis. Menoufia Med J [serial online] 2019 [cited 2019 Nov 12];32:1104-7. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/1104/268852




  Introduction Top


Tuberculosis (TB) is a major cause of death around the world. One of the most important and common complaints of patients with TB which also affects the immune status is weight loss [1]. When TB infection occurs, a variety of chemokines and cytokines are secreted from infected cells and tissue macrophages. Tumor necrosis factor-α (TNF-α) increases early in the disease and takes part in the pathogenesis and prevention of mycobacterial infection. TNF-α also appears crucial for the formation of Mycobacterium tuberculosis-constraining granulomas, infection control, and elimination of mycobacteria [2]. Some cytokines promote inflammation and are called proinflammatory cytokines [TNF-α, interleukin (IL)-1, IL-6, and IL-8], whereas other cytokines suppress the activity of proinflammatory cytokines and are called anti-inflammatory cytokines (IL-4, IL-10, and IL-13) [3]. Proinflammatory cytokines are responsible for weight loss associated with TB. TNF-α has some harmful effects such as acute-phase pathophysiologic events, including fever and tissue necrosis [3],[4].

The aim of this work was to investigate the relationship between serum TNF-α level and TB severity.


  Participants and Methods Top


This study was carried out in El-Mahala Chest Hospital during the period from April 2014 to June 2016. It included 50 participants divided into two groups. Group I included 40 adult patients newly diagnosed as having active pulmonary TB. The exclusion criteria were other causes of weight loss such as diabetes and lung cancer, hepatic and renal insufficiency, collagen diseases, and patients receiving or having received previous anti-TB therapy. Group II included 10 apparently healthy volunteers recruited from the outpatient clinic. After obtaining an informed consent, all participants were subjected to detailed history taking and physical examination including general and local examination. Calculation of BMI was as follows: BMI = weight (kg)/height (m 2). BMI categories were as follows: underweight = less than 18.5, normal weight = 18.5–24.9, overweight = 25–29.9, and obesity = BMI of 30 or greater [5]. Roentgenographic examinations included plain chest radiographies (posteroanterior and lateral views). Findings were classified into normal, minimal lesion, moderately advanced lesion, and far advanced lesion according to radiological classification of TB extent (National Tuberculosis Association of the USA) [6]. Mycobacteriological investigations included sputum smears examination (spontaneous or induced sputum): 3–5 samples were examined for the presence of acid-fast bacilli by Zeil–Neelsen stain. Laboratory investigations included complete blood picture, erythrocyte sedimentation rate, fasting serum glucose level and 2 h postprandial glucose level, kidney functions (urea and creatinine), liver functions (alanine aminotransferase, aspartate aminotransferase, and serum albumin), and serum TNF-α measurement by enzyme-linked immunosorbent assay.


  Results Top


Males constituted 75% of the patients and 25% were females. Smokers were 75% and nonsmokers were 25%.

The mean value of TNF-α was 17 832.00 ± 23 396.87 in TB cases before treatment. The mean value of TNF-α was 13 447.00 ± 4889.65 in TB cases after treatment, and in controls, it was 278.05 ± 142.58, with P value less than 0.01 [Table 1].
Table 1: Comparison between serum tumor necrosis factor-α among patients with tuberculosis (before and after starting treatment) and the control group

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There was a significant difference between serum TNF-α regarding symptomatology before and after treatment with a significant P value less than 0.001 [Figure 1].
Figure 1: Comparison of tumor necrosis factor-α level in different group of symptomatology.

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There was a negative correlation between serum TNF-α and BMI among cases, with a significant P value less than 0.05. There was a positive correlation between serum TNF-α and clinical severity among cases with a significant P value of 0.003. There was a positive correlation between serum TNF-α and radiological severity among cases, with P value less than 0.086 [Table 2].
Table 2: Correlations between serum tumor necrosis factor-α and BMI, clinical severity, and radiological severity among patients

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  Discussion Top


In the current study, there was a higher incidence of TB in males and in smokers. Sirelkhatim et al. [7] and Woodring et al. [8] reported that although there was little difference in susceptibility to TB between male and female patients, male patients are more affected than females, which might be owing to the environmental factors, as they are forced to work under hard conditions and consumed insufficient nutrients in comparison with the female patients, being mostly at home; moreover, specific biological sex-related factors may render men even more susceptible to pulmonary TB than women, as estradiol enhances macrophage activation [9]. There was a significant difference between the studied groups regarding TNF-α (P < 0.01) as shown in [Table 1]. Cakir et al. [10] found increased levels of TNF-α and leptin in patients with TB, with good correlation between these two parameters, and gave an explanation that the elevated leptin level leads to weight loss and may contribute to the inflammatory process. In previous studies done by Bekker et al. [11] and Silver et al. [12], there was an association between TNF-α production and M. tuberculosis virulence in human monocytes, as well as a correlation between the increase in serum TNF-α levels and the clinical deterioration in patients with a severe form of TB.

There was a significant difference between serum TNF-α regarding symptomatology before and after treatment, with a significant P value less than 0.001, as shown in [Figure 1]. This is supported by Mohan et al. [13], who found that TNF-α induces fever and weight loss, which are typical symptoms of TB. It has been shown to be associated with both protection and pathogenesis in mycobacterial infections as reported by Mohan et al. [13] and Moreira et al. [14]. Recent findings support the hypothesis that cytokine induction of leptin may play a significant role in anorexia and cachexia of inflammatory diseases and cancer. Microbial products and cytokines such as TNF-α and IL-1 increase leptin expression dose dependently in adipose tissue as demonstrated by Finck and Johnson [15].

Cakir et al. [10] speculated that serum TNF-α levels and leptin might be responsible for the weight loss in patients with pulmonary TB. Bekker et al. [11] observed worsening of clinical condition in 16 patients during the first 42 days of treatment, with two deaths among those having severe pulmonary TB. All patients had increased serum TNF-α and lactic acid levels.

There were a negative correlation between serum TNF-α and BMI in the studied groups (with a significant P < 0.05) as shown in [Table 2]. Recent findings support the hypothesis that cytokine induction of leptin may play a significant role in anorexia and cachexia of inflammatory diseases and cancer. Anorexia is a common finding that results in metabolic disturbances and weight loss during infective diseases. It has been suggested that weight loss in TB, which is one of the most severe infective diseases, may be owing to the effects of TNF-α, which was found to be increased in patients with active TB, as found by Chapman and Hall [16] and Beutler and Cerami [17].

There was a positive correlation between serum TNF-α and clinical severity in the studied groups (with a highly significant P = 0.003) as shown in [Table 2]. These results are in accordance with Andrade Júnior [18], who reported a correlation between serum TNF-α levels and clinical severity of TB. There was a positive correlation between serum TNF-α and radiological severity in the studied groups (P < 0.086) [Table 2]. Tsao et al. [19] published that the bronchoalveolar lavage fluid levels of TNF-α, IL-1, and IL-6 were all significantly higher in patients with large cavities than in patients without cavities or with smaller cavities. Kart et al. [20] found that the levels of TNF-α, IL-4, and soluble IL-2R are related with each other and also evaluated the levels of TNF-α, IL-4, and sIL-2R after anti-TB therapy and relation with radiologic scores. The TNF-α level was not statistically different in the four radiological groups before and after chemotherapy. Assessment of the level of serum TNF-α as a factor in the development of TB, worsening of the clinical outcome in patients with TB who presented with higher TNF-α serum levels, and also as responsible for the weight loss in patients with pulmonary TB can be helpful.


  Conclusion Top


Serum TNF-α levels were elevated in patients with TB compared with controls. There was a highly significant negative correlation between TNF-α level and BMI. Serum TNF-α had insignificant positive correlation with grades of Ziehl–Neelsen stain and chest radiography, and the cut-off points of TNF-α were found to be 618.1 pg/ml.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Silver RF, Li Q, Ellner JJ. Expression of virulence of Mycobacterium tuberculosis within human monocytes: virulence correlates with intracellular growth and induction of tumor necrosis factor alpha but not with evasion of lymphocyte-dependent monocyte effector functions. Infect Immun 1998; 66:1190–1199.  Back to cited text no. 12
    
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Mohan VP, Scanga CA, Yu K, Scott HM, Tanaka KE, Tsang E, et al. Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology. Infect Immun 2001; 69:1847–1855.  Back to cited text no. 13
    
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Moreira AL, Tsenova-Berkova L, Wang J, Laochumroonvorapong P, Freeman S, Freedman S, et al. Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis. Tuber Lung Dis 1997; 78:47–55.  Back to cited text no. 14
    
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Finck BN, Johnson RW. Tumor necrosis factor (TNF)-α induces leptin production through the p55 TNF receptor. Am J Physiol Regul Integr Comp Physiol 2000; 278:R537–R543.  Back to cited text no. 15
    
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Andrade Júnior DRD, Santos SAD, Castro ID, Andrade DR. Correlation between serum tumor necrosis factor alpha levels and clinical severity of tuberculosis. Braz J Infect Dis 2008; 12:226–233.  Back to cited text no. 18
    
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Tsao TC, Hong JH, Li LF, Hsieh MJ, Liao SK, Chang KS. Imbalances between tumor necrosis factor-alpha and its soluble receptor forms, and interleukin-1 beta and interleukin-1 receptor antagonist in BAL fluid of cavitary pulmonary tuberculosis. Chest J 2000; 117:103–109.  Back to cited text no. 19
    
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Kart L, Buyukoglan H, Tekin IO, Altin R, Senturk Z, Gulmez I, et al. Correlation of serum tumor necrosis factor-alpha, interleukin-4 and soluble interleukin-2 receptor levels with radiologic and clinical manifestations in active pulmonary tuberculosis. Mediators Inflamm 2003; 12:9–14.  Back to cited text no. 20
    


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