Interleukin 2 and IL-15 are two closely related cytokines, displaying important functions in the immune system. They share the heterodimeric CD122/CD132 receptor to deliver their signals within target cells. Their specificity of action is conferred by their α receptor chains, IL-2Rα and IL-15Rα. By combining an increased affinity for CD122 and an impaired recruitment of CD132, we have generated an original molecule named IL-2Rβ/γ (CD122/CD132) inhibitor (BiG), targeting the CD122/CD132 receptor. BiG efficiently inhibited IL-15- and IL-2-dependent functions of primary cells, including CD8 T and NK cells, in vitro and in vivo. We also report a differential dynamic of action of these cytokines by highlighting a major role played by the IL-2Rα receptor. Interestingly, due to the presence of IL-2Rα, BiG had no impact on IL-2-dependent regulatory T cell proliferation. Thus, by acting as a fine switch in the immune system, BiG emphasizes the differential roles of these two cytokines.

Background Clinical Practice Guidelines endorse using ambulatory blood pressure monitoring (ABPM) for the diagnosis and management of hypertension (HTN). However, ABPM is not always tolerated by patients, and differences between individuals according to age and sex remain unexplored. Methods This is a post-hoc analysis of a prospective, single-arm clinical trial (NCT03920956) that evaluated the feasibility of an ABPM service provided at two community pharmacies. Tolerability was assessed using a previously published survey, which included seven yes/no questions and eight answered on a scale of 0-10. Descriptive statistics and Chi-square analyses were used to summarize the data for the patient surveys and to describe sex and age differences in device tolerability. Results Of the 52 subjects enrolled, 50 (96%) completed the survey; half were female with a mean (SD) age of 57.5 years (15.8). Chi-square analyses showed that compared to their male counterparts, females were more likely to find the monitor cumbersome to wear (76.2% vs. 40%, p = 0.014). Subjects under 55 years of age were more likely to be disturbed by the noise of the monitor during driving (38.1% vs. 4.2%, p = 0.005) and at other times (35.0% vs. 8.3%, p = 0.029), and to find the monitor embarrassing to wear (33.3% vs. 7.1%, p = 0.019). Conclusions Although ABPM was generally well-tolerated overall, we did identify age and sex differences in tolerability. These factors should be considered to ensure patient acceptance and tolerability of ABPM.