In this paper, Cinimo et al. explore the role of the TGFβ-family protein GDF15 in activation of the hypothalamic–pituitary–adrenal (HPA) axis. During infection, cytokines such as TNFα/β, IL-1 and IL-6, activate the HPA axis. This increases circulating glucocorticoids, which have anti-inflammatory, metabolic, and vasomotor effects. However, O’Rahilly lab have determined that in response to stimuli such as toxins, which don’t provoke an inflammatory response, the primary activator of the HPA axis is GDF15. GDF15 is an intriguing protein also being explored as an anti-obesity therapeutic target, these findings may have a pivotal impact on future clinical study design and open new avenues of investigation. Certainly cool science!