The beneficial effects of adjunctive recombinant human interleukin-2 for multidrug resistant tuberculosis

Abstract

IntroductionMultidrug-resistant tuberculosis (MDR-TB) is a hard-to-treat disease with a poor outcome of chemotherapy. In the present study, the efficacy and safety of recombinant human interleukin-2 (rhIL-2) were investigated in patients with MDR-TB.Material and methodsFifty culture-confirmed patients with MDR-TB were included. Twenty-five patients were randomly assigned to the trial group (injection of 500 000 IU of rhIL-2 once every other day at the first, third, fifth and seventh months in addition to standard multidrug therapy) and another 25 patients to the control group with standard multidrug therapy. All patients were monitored clinically, and T-cell subsets were analyzed by flow cytometry.ResultsThe rates of sputum negative conversion and X-ray resolution in the trial group were higher than those of the control, and the improvements were significant by completion of treatment. In addition, CD4+CD25+ T cells in the controls rose gradually during treatment. The levels at the end of the seventh month were significantly higher than before, which were also significantly different when compared with those from the trial group at the same time. However, there were no such changes associated with treatment in the trial group. No significant differences appeared in other T cell subsets.ConclusionsExogenous IL-2 in the present regimen improves immunity status. Adjunctive immunotherapy with a long period of rhIL-2 is a promising treatment modality for MDR-TB.

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis

“…The therapeutic use of IL-2 in various human cancers has been long documented, being indispensable for T-cell proliferation directed against transformed cells ( Rosenberg, 2014 , Quattrocchi et al, 1999 , Sakamoto et al, 2011 , Takayama et al, 1991 ). Patients with chronic infectious disease indications, characterized by impaired and/or dysfunctional T-cell responses such as pulmonary tuberculosis and viral hepatitis, may also benefit from IL-2 therapy ( Shen et al, 2015 , Tomova et al, 2009 ) in part by reconstituting the T-cell receptor zeta chain (TCRζ) expression, a pivotal link for T-cell activation and ‘immune fitness’. IL-7 has been shown to increase expansion of circulating human CD4 and CD8 T cells, with a positive effect on T-cell receptor (TCR) repertoire diversification and reduction in Treg numbers ( Sportes et al, 2008 ).…”

Host-Directed Therapeutic Strategies for Tuberculosis

“…A randomized controlled clinical trial to test the efficacy of adjunctive IL-2 supplementation with standard anti-TB therapy did not show significant clinical benefits, compared to treatment with antibiotics without IL-2 ( 107 ). Interestingly, in a recent clinical study carried out with 50 MDR-TB patients, adjunct supplementation of recombinant human IL-2 (500,000 IU in alternative days and months up to 7 months) in improved immunity status and sputum smear conversion ( 108 ) (Table 2 ). These observations not only highlight the complex roles of cytokines in regulating immune cell functions but also the potential of modulating cytokine activities as HDT for TB treatment.…”

Immunotherapy for tuberculosis: future prospects

“… 70 Despite some controversial results regarding the effects of IL-2 tested in new TB cases, 71 , 72 intradermal injection of 500,000 IU of IL-2 every other day at the first, third, fifth, and seventh months of drug treatment of 25 MDR-TB patients led to a higher rate of sputum conversion compared to controls receiving only drug-treatment. 73 IL-2 also enhanced the activities of a pyrophosphate to enhance γδ T-cell responses and decrease residual M. tuberculosis in the lungs of infected monkeys. 74 Anti-TNF-α antibodies which are commonly used for treatment of severe rheumatological disorders increase the risk of reactivation of TB.…”