Hormone substitution as abates inflammation—is clinical implementation yet indicated?

In this issue of the journal, de Sousa et al. [1] present an experimental study on the impact of a therapeutic administration of 17β-oestradiol (E2) on the systemic and local pulmonary inflammatory response during reperfusion after temporary ischaemia triggered by aortic balloon occlusion in a male rat model. The authors are confirming the known systemic inflammatory response associated with increased microvascular permeability triggered by simulated distal circulatory arrest. In the second step, they experimentally demonstrate that the administration of E2 during reperfusion can attenuate the inflammatory reaction systemically by a reduction of CINC-1 and locally through a reduction of MPO, IL-1β and IL-10 in lung tissue. Previously, the group already investigated the effects of E2 administration prior to ischaemia induction in the same experimental model demonstrating analogously positive immune-modulatory effects [2]. Therefore, the present study is further advancing the understanding of the debated effect of perioperative hormone administration on alleviating the deleterious effects of pulmonary reperfusion injury. The potential clinical implication is significant, if the rat model can be translated into the clinical scenario of respiratory failure after major aortic surgery in both elective or emergency cases, currently affecting up to 14% of patients [3, 4]. However, ischaemia–reperfusion injury is only 1 pathomechanism involved in respiratory and systemic inflammation in these frequently complex patients with numerous co-morbidities. Moderate systemic hypothermia—routinely utilized in clinical practice—has been suggested to have similar effects: the group of Kang et al. [5] investigated the effect of systemic hypothermia in thoracic aortic ischaemia–reperfusion in a mouse model, showing a significantly lower lung MPO level in mice with aortic occlusion at 34°C (compared to 38°C).