Pulmonary arterial hypertension and the Enigma code of smouldering inflammation

Abstract

“What causes fever?” was the question that prompted the work that led to the discovery of the “leukocyte pyrogen”, eventually named interleukin (IL)-1, in the late 1970s [1]. However, despite the rapid understanding of innate and adaptive immune responses and inflammation during the 1980s, it was not until 1995 that Humbert et al. [2] reported that both IL-1 and IL-6 levels were increased in the plasma of patients with idiopathic pulmonary arterial hypertension (PAH), thus revealing an inflammatory component in the pathogenesis of severe PAH. Ever since the first report by Humbert et al. [2], the role of inflammation as a cause or consequence of PAH has remained controversial [3] and this ongoing debate has perhaps prevented the pragmatism to design clinical trials to test novel anti-inflammatory therapies in patients with PAH. Anti-interleukin-1 treatment for pulmonary arterial hypertension: are we there yet? The authors wish to thank Charles A. Dinarello (University of Colorado, Denver, CO, USA) for his critical reading of this manuscript.