Dataset Information

Therapeutic effects of recombinant human interleukin 2 as adjunctive immunotherapy against tuberculosis: A systematic review and meta-analysis.

ABSTRACT:

Background

Interleukin 2 (IL-2) is a cytokine secreted by activated T cells. Studies exploring recombinant human interleukin 2 (rhuIL-2) as an adjunctive immunotherapeutic agent to treat tuberculosis (TB) have shown variable results; however, the true therapeutic efficacy of rhuIL-2 administration in TB patients has not been determined.

Methods

A systematic review to identify publications exploring the association between rhuIL-2-based immunotherapy for TB and outcomes (sputum culture conversion, sputum smear conversion, radiographic changes, and leukocyte phenotype changes) in patients with pulmonary TB published before June 8, 2018 was performed. Data were extracted and analyzed by two investigators independently.

Results

A total of 2,272 records were screened. Four randomized controlled trials (RCTs) comprising 656 pulmonary TB patients were finally included. The rhuIL-2 treatment could significantly improve the sputum culture conversion of TB (RR, 1.18; 95%CI: 1.03-1.36; I2 < 0.01; P = 0.019) after at least 3 months of anti-TB therapy and the sputum smear conversion of TB during anti-TB therapy. Treating multidrug-resistant tuberculosis (MDR-TB) with rhuIL-2 could improve the sputum culture conversion (RR, 1.28; 95%CI: 1.05-1.57; I2 < 0.01; P = 0.016) and smear conversion (RR, 1.28; 95%CI: 1.09-1.51; I2 < 0.01; P = 0.003) at the end of anti-TB treatment. Meanwhile, rhuIL-2-based adjunctive immunotherapy could expand the proliferation and conversion of CD4+ and natural killer (NK) cells. Three of the included studies suggested that radiographic changes could not be improved by the use of rhuIL-2 as adjunctive immunotherapy. Publication bias did not exist.

Conclusions

Based on this first meta-analysis, rhuIL-2-based adjunctive immunotherapy appears to expand the proliferation and conversion of CD4+ and NK cells, as well as improve the sputum culture (at 3 months and later) and smear conversion of TB patients.

SUBMITTER: Zhang R

PROVIDER: S-EPMC6053227 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Therapeutic effects of recombinant human interleukin 2 as adjunctive immunotherapy against tuberculosis: A systematic review and meta-analysis.

Zhang Ruimei R Xi Xiangyu X Wang Chunying C Pan Yong Y Ge Changhua C Zhang Liying L Zhang Shuo S Liu Huimei H

PloS one 20180719 7

<h4>Background</h4>Interleukin 2 (IL-2) is a cytokine secreted by activated T cells. Studies exploring recombinant human interleukin 2 (rhuIL-2) as an adjunctive immunotherapeutic agent to treat tuberculosis (TB) have shown variable results; however, the true therapeutic efficacy of rhuIL-2 administration in TB patients has not been determined.<h4>Methods</h4>A systematic review to identify publications exploring the association between rhuIL-2-based immunotherapy for TB and outcomes (sputum cul ...[more]

PMID: 30024982

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Project description:BackgroundInterleukin-6 (IL-6) has undeniable roles in inflammatory processes due to autoimmune diseases. In this regard, soluble receptors are considered a potential approach to mitigate its inflammatory effects and modulate its physiological effects by reducing the IL-6 binding to cell surface-specific receptors.ObjectiveThis study aimed to produce IL-6 receptor (IL-6R) in soluble form with enhanced affinity to IL-6 without signal transduction ability.Materials and methodsThe 3D structure of IL-6R with the selective mutations for enhancing the IL-6 binding, with minimum ability to signal transduction (mIL-6R), was predicted using Modeller 9.19. This mutated form was docked to IL-6 and gp130 (a part of the native IL-6 receptor involved in signal transduction) by the HADDOCK2.2 web server. The expression of mIL-6R was performed in E. coli BL21 (DE3), using pTWIN-1 plasmid as its linkage to the Ssp Intein. IMPACT system manual was used to purify the protein at 25 °C overnight. Next, ELISA was performed to compare the affinity of mutated and native IL-6R to IL-6. Finally, A549 cells were used to compare the inhibition of cytotoxic effects of native and mutated IL-6R.ResultsIn the silico section, results established the stability of mutant's structure with more and less affinity to IL-6 and gp130, respectively. The expression and purification results showed bands of about 50 and 23 kDa, representing the correct size of the Intein1-mIL-6R fusion protein and cleavaged mIL-6R in SDS-PAGE, respectively. Furthermore, a significant enhancement in the affinity of mutated IL-6R to IL-6 was observed compared to the native receptor. Finally, A549 cells showed more cytotoxic effects followed by treating with mutated IL-6R in comparison to cells treated with native soluble IL-6R.ConclusionThe recombinant production of a mutated form of IL-6R with the potential ability to antagonize the IL-6 inflammatory effects confirmed with in silico studies was successfully performed for the first time to create a new drug candidate for suppressing the inflammatory effects of IL-6.

Dataset Information

Therapeutic effects of recombinant human interleukin 2 as adjunctive immunotherapy against tuberculosis: A systematic review and meta-analysis.

Background

Methods

Results

Conclusions

Publications

Therapeutic effects of recombinant human interleukin 2 as adjunctive immunotherapy against tuberculosis: A systematic review and meta-analysis.

Similar Datasets

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