Clinical efficacy of thymosin alpha 1 combined with multi-modality chemotherapy and its effects on immune function of patients with pulmonary tuberculosis complicated with diabetes.

Li Wu,Yan-Hong Tian,Yan-Li Zhang,Lai-Yin Chen,Pei-Pei Luo

doi:10.12669/pjms.38.1.4419

Abstract

ABSTRACTObjective:To observe the clinical efficacy of thymosin alpha 1 (Tα1) combined with multi-modality chemotherapy in patients with pulmonary tuberculosis (PTB) complicated with diabetes and discuss the effects of such combination therapy on lymphocyte subsets and sputum levels of cytokines.Methods:A total of 120 patients with PTB complicated with diabetes admitted to the Affiliated Hospital of North China University of Science and Technology from January 2017 to January 2018 were included in this study and randomly divided into an experimental group (Tα1 group, n=60) and a control group (n=60). Clinical efficacy and adverse drug reactions were observed and compared between the two groups. Blood samples were collected for lymphocyte (NK cell and T cell subsets) levels by flow cytometry, and sputum samples were collected for cytokine (IL-2, IFN-γ, IL-4 and TNF-α) levels by ELISA.Results:Two groups showed no statistically significant difference in sputum culture-negative conversion rate, chest lesion absorption rate, and cavity closure rate (P>0.05) after 6 months of treatment. However, after 12 months, the sputum culture-negative conversion rate, chest lesion absorption rate, and cavity closure rate in the Tα1 group increased compared with the control group, and the differences were statistically significant (P<0.05). There was a significant increase in CD3+, CD4+, NK-cells lymphocytes after six months in the Tα1 group than in the control group, whereas the CD8+, Th17, Treg lymphocytes in the Tα1 group were substantially lower than in the control group, with the differences showing statistical significance (P<0.05, respectively). After six months of treatment, the sputum supernatant levels of interleukin-4 (IL-4) and tumor necrosis factor α (TNF-α) in the Tα1 group were lower than in the control group, whereas the sputum supernatant levels of interleukin-2 (IL-2) and interferon gamma (IFN-γ) in the Tα1 group were higher than in the control group, and the differences were statistically significant (P<0.05, respectively). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05).Conclusion:Tα1 combined with multi-modality chemotherapy has a visible curative effect on PTB patients with diabetes as it can regulate immune function and reduce the levels of inflammatory cytokines. As a safe combination therapy, it seems promising for further use in clinical practice.

Highlights

As pointed out by the WHO in the Global Tuberculosis (TB) Report 2012, China is heavily burdened with TB.[1]
If an individual does not timely receive effective treatment, Pulmonary tuberculosis (PTB) can lead to cavity expansion and focal fibrosis due to adverse drug reactions, bacterial variation, hepatitis B virus (HBV), human immunodeficiency virus (HIV), or diabetes.[2]
Inclusion criteria: A patient was considered eligible for the clinical trial if he/she: 1. Was confirmed to have PTB and diabetes according to the WS 288-2008 Diagnostic criteria for pulmonary tuberculosis[9] and the 2014 American Diabetes Association (ADA) diabetes guidelines;[10 2]

Summary

Introduction

As pointed out by the WHO in the Global Tuberculosis (TB) Report 2012, China is heavily burdened with TB.[1]. If an individual does not timely receive effective treatment, PTB can lead to cavity expansion and focal fibrosis due to adverse drug reactions, bacterial variation, hepatitis B virus (HBV), human immunodeficiency virus (HIV), or diabetes.[2] Clinically, medication remains the mainstay of treatment for patients with PTB, in which case, the curative effect, and clinical prognosis are strongly affected by the relatively long course of treatment and high drug tolerance.[3,4] Diabetes is a contributory factor for impairment of the immune mechanism, hypofunction of the immune system, and an increased risk of TB infection.[5] In addition to abnormal carbohydrate metabolism, diabetes is associated with lipid and protein metabolism at an accelerated speed This creates a favorable environment for the growth of M. tb and reduces the curative effect of anti-TB treatment for PTB patients with diabetes.[6] Thymosins are small molecular polypeptide secreted by thymus tissue, which modulate both innate and adaptive immunity, can reverse T cell failure and restore immune reconstruction.[7] Thymosin alpha 1 (Tα1) and thymopentin (TP5) are two thymus-derived immunomodulatory agents. Immunomodulatory role of thymosin is established in microbial infections and in malignancy, pancreatic lesions, diabetes, immunodeficiencies, and vaccine efficacy etc.[8]

Methods

Results

Conclusion