Recombinant interleukin-7 treatment of refractory

Background: Nontuberculous mycobacteria disease is an emerging opportunistic infection that is often refractory to therapy. Interleukin 7 (IL-7) is a pleiotropic cytokine with broad-ranging effects that enhance immunity and augment monocyte/macrophage anti- Objectives: This study evaluated IL-7 in patients with refractory Design: Prospective, single-center, randomized, study of IL-7 in patients with refractory MAC-LD. Methods: Randomization (two sets of 4 weekly IL-7 injections) was stratified based on the presence of pulmonary cavities. The primary outcome was sputum culture conversion to negative within 6 months. Exploratory outcomes included investigation of potential molecular mechanisms of immunosuppression via single-cell RNA sequencing (scRNA-seq). Results: Of the eight participants enrolled, six completed the IL-7 regimen, one completed one 4-week therapy, and one received a single dose of IL-7. All six participants who completed the regimen showed an increased absolute lymphocyte count (ALC), yet none converted their sputum culture to negative at 6 months. Similarly, there were no differences in secondary outcomes compared to baseline. IL-7 was well tolerated, and two participants showed an increase in time-positivity for MAC in their sputum culture. scRNA-seq revealed increased expression of genes involved in immunosuppressive pathways. Conclusion: In adults with refractory MAC-LD, IL-7 did not result in sputum culture conversion. IL-7 reversed the underlying lymphopenia associated with MAC-LD and led to a sustained increase in ALC. The study was limited by a small sample size, and although a longer course of IL-7 combined with newer antimicrobials for may warrant further investigation, structural lung disease may be a stronger predictor of cure than immune dysfunction in MAC-LD. Trial registration: The trial was registered in clinicaltrials.gov (NCT04154826).