Inflammation-mediated skeletal muscle atrophy is a feature of cachexic clinical conditions such as cancer, chronic obstructive pulmonary disease (COPD) and chronic kidney disease. It is now also considered to be one aetiological feature of the age-related loss of skeletal muscle mass and quality – sarcopenia. Such loss of lean body mass is associated with poor morbidity and mortality outcomes (1). Studies in murine cell lines and in mouse models suggest that IL-15 promotes myogenesis and may protect against inflammation-mediated skeletal muscle atrophy (2-4). However, the effects of IL-15 on human skeletal muscle growth and development remain largely uncharacterised. In this study, primary human myoblasts were cultured from skeletal muscle biopsies obtained from young (age 18-30), healthy subjects. Differentiating primary human myoblasts were stimulated with human recombinant IL-15 (rIL-15) for 8 d, with or without the addition of 1 ng/mL recombinant TNFα (rTNFα). Differentiated myotubes were immunofluorescence stained for desmin, counterstained with DAPI and imaged on an epifluorescence microscope. Myoblast nuclear fusion and myotube thickness were quantified using ImageJ software. Accompanying changes in myogenic gene expression were quantified by SYBR green RT-qPCR. All data are presented as mean ± SEM, n=3 biological replications (technical replications are detailed in the figure legend) and were analysed by one-way ANOVA with post-hoc Bonferroni correction unless otherwise indicated. rIL-15 (100 ng/mL) increased the thickness of differentiated myotubes by 22 ± 5 % (p <0.01 by Mann-Whitney U test with post-hoc Holm’s sequential Bonferroni adjustment), compared to unstimulated control myotubes (see figure). rIL-15 at either 25 or 100 ng/mL also enhanced the nuclear fusion of myoblasts (35 ± 4 %, p < 0.0001; 45 ± 7 %, p < 0.0001), compared to unstimulated controls (see figure). Stimulation of confluent myoblasts with 25 ng/mL rIL-15 induced a small (1.29 fold) but highly significant (p < 0.0001) increase in the expression of myomaker, a cell membrane protein essential for myoblast fusion. rTNFα (1 ng/mL) induced a 30 ± 5 % decrease in myotube thickness (p < 0.0001) compared to an unstimulated control. Co-incubation of differentiating myoblasts with rIL-15 and rTNFα partially reversed this effect, limiting the reduction in myotube thickness to 11 ± 6 % of the control, a significant improvement compared to the rTNFα condition (p = 0.013). In summary, we have demonstrated that rIL-15 enhances myogenesis and that such stimulation can partially reverse the deleterious effects of rTNFα on human myotube development. IL-15 may be an effective therapeutic target for inflammation-mediated skeletal muscle atrophy.