Abstract
It is urgent to find an optimised therapy regimen for the control of MDR-TB globally. This study aimed to evaluate the efficiacy and safety of a combined regimen of rhIL-2 injection and standard chemotherapy within 18-month duration in a randomized controlled trial conducted in 14 centres in eastern China. From Jan. 2009 to July. 2016, 271 MDR-TB cases were enrolled and followed up in two groups, 142 cases in study group while 129 cases in control group. Clinical efficacy, safety and immune activity (Th1, Th17, Treg, IFN-γ, IL-17) among the two groups were evaluated and compared. After 24-month following up, cure rate in IL-2 group show higher than that in control group (56% VS 36%, P < 0.01). Rate of mycobacterium clearance (sputum negative) within 3 months was significantly higher in IL-2 group (74% VS 59%, P < 0.05) with no adverse events raised. Patients after rhIL-2 treatment showed increasing of Th1 populations and decreasing of Th17 and Regulatory T cells (Treg) populations, while levels of IL-17A, ROR-γt, and Foxp3 mRNA decreased and level of IFN-γ mRNA increased in PBMCs. Thus, rhIL-2 combined regimen within shorter duration achieved high conversion and success rates and improved Th1/Th17 immune responses, with no safety concerns emerging in MDR-TB patients.
Highlights
IL-2 is a pleiotropic cytokine that is produced after antigen activation and plays crucial roles in the immune response[5,6,7,8]
When we designed the trial to determine the clinical effect of rhIL-2 adjunctive immunotherapy in MDR-TB, few large-scale clinical trials had tested and compared the effect of a shorter course of immunotherapy regimen to a 24 month-course of standard chemotherapy regimen in MDR-TB patients
In 1997 Johnson et al conducted another pilot study, totally about 20 MDR-TB patients were devided to 3 groups with treatment schedules induced different results, showing that proportion of patients receiving daily rhIL-2 therapy or 5 days followed by a 9-day ‘rest’, for three cycles pulse rhuIL-2 treated demonstrated reduced or cleared sputum bacterial load significantly[24]
Summary
IL-2 is a pleiotropic cytokine that is produced after antigen activation and plays crucial roles in the immune response[5,6,7,8]. We hypothesized that IL-2 play a crucial role in modulating Th17, Treg cells responses in patients with MDR-TB, thereby maintaining the balance between protection and pathology, www.nature.com/scientificreports/. The aim of the present study is to evaluate the safety, tolerability and effectiveness of the novel rhIL-2 within background regimens in a large multicentre cohort of MDR-TB patients treated under two treatment arms (rhIL-2 within chemotherapy regimen vs chemotherapy regimen). We first launched the present pilot study by investigating the kinetics of the activation of Th1, Treg, and Th17 cells from these patients in different stages of regimen by flow cytometry and evaluating the mRNA levels of their homologous cytokines by qRT-PCR as immune parameters to shed light on the mechanisms underlying the beneficial effect of rhIL-2 immunotherapy which still remained incompletely understood
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