Growth Differentiation Factor (GDF)-15 in Pulmonary and Critical Care Medicine

Growth differentiation factor 15 (GDF-15) acts both as a stress-induced cytokine with diverse actions at different body sites and as a cell-autonomous regulator linked to cellular senescence and apoptosis. For multiple reasons, this divergent transforming growth factor (TGF)-β molecular superfamily member should be better known to pulmonary researchers and clinicians. In ambulatory individuals, GDF-15 concentrations in peripheral blood are an established predictive biomarker of all-cause mortality and of adverse cardiovascular events. Concentrations on admission of critically ill patients (without or with sepsis) correlate with organ dysfunction and independently predict short- and long-term mortality risk. GDF-15 is a major downstream mediator of p53 activation, but can also be induced independently of p53, notably by non-steroidal anti-inflammatory agents. GDF-15 blood concentrations are markedly elevated in adults and children with pulmonary hypertension. Levels are also increased in chronic obstructiv...