Original ArticleClinicalAssessment of Serum IL-1, IL-2 and IFN-γ Levels in Untreated Pulmonary Tuberculosis Patients: Role in Pathogenesis
Introduction
In tuberculosis (Tb) infection, a majority of individuals exposed to its etiological agent Mycobacterium tuberculosis (MTb) become infected and receive protection from developing into an active disease. This resistance to mycobacterial infection is because of the interaction between macrophages and T-cells, dependent on interplay of cytokines produced by each cell (1). Cytokines have been implicated in the protective immunity, pathophysiology and development of Tb (2). Many aspects of cytokine dynamics in patients with active Tb have been investigated. However, studies on understanding of how cytokine production would contribute to host defense and to immune-pathogenesis of Tb still remain to be understood (3). Functionally, Th1 cells (secreting IL-2, IFN-γ) are associated with cell-mediated immune responses (delayed type of hypersensitivity and in macrophage activation), whereas Th2 cells are associated with humoral immunity (4). IFN-γ plays an important role in conferring protection to the host by activating (infected) macrophages to kill intracellular mycobacteria effectively, as well as in regulation and enhanced expression of MHC class II molecules involved in antigen recognition 5, 6. IFN-γ is produced by activated CD4+ cells. For activation of CD4+ cells, IL-2 is required and its synthesis is induced by proinflammatory cytokines such as IL-1, produced from macrophages infected with MTb. IL-1 acts on resting CD4+ cells to express IL-1 receptor and activates to produce IL-2 (7). Thus, produced IL-2 (also known as T-cell growth factor, produced by certain subsets of T-cells) is an immunomodulatory factor and has been shown to promote long-term growth of activated CD4+ T-cells and induction of IFN-γ (8).
In the present study, levels of IL-1, IL-2 and IFN-γ were determined in serum of untreated pulmonary Tb patients, apparently healthy/contacts and in normal healthy individuals with an objective of understanding defect(s), if any, in synthesis of any of these cytokines that may lead to development of disease.
Section snippets
Study Population
Sera were obtained from the following groups of patients: Group I (n = 33), untreated pulmonary Tb confirmed by clinical and radiological (chest X-ray) findings along with identification of acid-fast bacilli (AFB) in sputum by microscopy (Ziehl–Neelsen Staining); Group II (n = 19), apparently healthy controls or contacts, and Group III (n = 20): normal healthy blood donors. Mean age of Group I patients was 42.28 years (range: 18–63 years, 31 male and two female patients). Mean age of Group II
Results and Discussion
Results obtained are shown in Figure 1. Levels of serum IL-1 found in Tb patients were significantly higher than in apparently healthy individuals/contacts (p <0.01) and in normal/healthy individuals (p <0.05). Higher levels of IL-1 in active Tb are likely to be involved in directing granuloma formation and control of M. tuberculosis infection (10). IL-1, a pro-inflammatory cytokine, released primarily from macrophages and many other cell types at the site of infection is involved in regulation
Acknowledgments
Financial support from the Department of Science and Technology (STEC), Government of Kerala State, Thiruvananthapuram is gratefully acknowledged. The authors thank Dr. Narayana Das, Medical Officer, Ms. Eva and other staff members of the State Tuberculosis Hospital, Trivandrum for their assistance in obtaining and as well as volunteering blood samples for the study. The authors thank the Director, SCTIMST, Trivandrum for providing the facility to carry out this study.
References (25)
- et al.
Cytokine profiles using whole blood assays can discriminate between tuberculosis patients and healthy endemic controls in BCG-vaccinated population
J Immunol Methods
(2002) - et al.
Circulating profile of Th1 and Th2 cytokines in tuberculosis patients with different degrees of pulmonary involvement
FEMS Immunol Med Microbiol
(1997) - et al.
Elevated levels of serum macrophage inhibitory factor in patients with pulmonary tuberculosis
Clin Immunol
(2002) - et al.
Functions of T-cell subsets and cytokines in mycobacterial infection
Eur Respir J
(1995) - et al.
Dynamics of cytokine generation in patients with active pulmonary tuberculosis
Curr Opin Infect Dis
(2003) Review: The immune response in human tuberculosis—implications for tuberculosis control
J Infect Dis
(1997)- et al.
Th1 and Th2 cells: different patterns of lymphocyte secretion lead to functional properties
Annu Rev Immunol
(1989) - et al.
T-cell responses to Mycobacterium tuberculosis
J Infect Dis
(1993) - et al.
The immunology of mycobacterial diseases
Am Rev Respir Dis
(1986) Interleukin-1
Interleukin-2 and the interleukin-2 receptor
Increased release of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha by bronchoalveolar cells lavaged from involved sites in pulmonary tuberculosis
Am J Respir Crit Care Med
Cited by (21)
Modulation of iron status biomarkers in tuberculosis-diabetes co-morbidity
2018, TuberculosisCitation Excerpt :On the other hand, sTfR displayed no significant differences between the groups. Other immunological studies from HIV infected patients also report that altered host iron status characterized by low transferrin has been identified as a risk factor for progression to TB among HIV-infected individuals [30]. These results indicate that altered levels of iron status markers are associated with iron homeostasis and inflammation in PTB patients with and without DM.
Efficacy and safety of interferon-gamma-targeted therapy in Crohn's disease: A systematic review and meta-analysis of randomized controlled trials
2013, Clinics and Research in Hepatology and GastroenterologyCitation Excerpt :However, these results need to be interpreted with caution due to several limitations. First, IFN-gamma is involved in host defenses and anti-inflammatory effects in certain situations [36–38]. Long-term inhibition of IFN-gamma might predispose patients to infections or exacerbate disease manifestations in some patients.
Helminths and skewed cytokine profiles increase tuberculin skin test positivity in Warao Amerindians
2012, TuberculosisCitation Excerpt :Finally, we used a multivariable modeling approach taking into account other putatively influencing factors, such as parasitic infections, demographic characteristics, nutritional status, other cytokine profiles, and the clustering at the household level. The univariate approach that was used in most other studies42–44,53 could have contributed to insufficient insight into the actual status of the cytokine network. We observed that the interactions between A. lumbricoides infection and IL-10- and Th2-dominated profiles were significantly associated with TST positivity.
Identification of biomarkers for sarcoidosis and tuberculosis of the lung using systematic and integrated analysis
2020, Medical Science MonitorImmunological recovery in patients with pulmonary tuberculosis after intensive phase treatment
2018, Journal of International Medical Research