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

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; I(2) < 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; I(2) < 0.01; P = 0.016) and smear conversion (RR, 1.28; 95%CI: 1.09–1.51; I(2) < 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.