Original Article
Clinical
Assessment of Serum IL-1, IL-2 and IFN-γ Levels in Untreated Pulmonary Tuberculosis Patients: Role in Pathogenesis

https://doi.org/10.1016/j.arcmed.2011.04.012Get rights and content

Background and Aims

Tuberculosis (Tb) infection is controlled by cell-mediated immunity through mediation of IL-1, IL-2 and IFN-γ. In this study IL-1, IL-2 and IFN-γ were determined in serum samples of untreated pulmonary Tb and control group including apparently healthy individuals or contacts and normal healthy blood donors with an objective of understanding defect(s), if any, in synthesis of any of these cytokines that may lead to a diseased state of Tb.

Methods

IL-1, IL-2 and IFN-γ were measured in serum samples of untreated Tb patients (n = 33), contacts (n = 19) and healthy individuals (n = 20) by commercially available monoclonal antibody-based ELISA.

Results

Statistically significant differences in IL-1 and IFN-γ concentrations between groups of pulmonary Tb and controls were observed, whereas no significant difference in IL-2 was seen.

Conclusions

In the present study, increased levels of cytokines in patients with pulmonary Tb are indicative of Th1 response. An increased level of cytokine (IFN-γ) in patients with untreated pulmonary Tb appears to be functionally defective.

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.

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