Interferon-β attenuates lung inflammation following experimental subarachnoid hemorrhage

Abstract

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) affects relatively young people and carries a poor prognosis with a case fatality rate of 35%. One of the major systemic complications associated with SAH is acute lung injury (ALI) which occurs in up to one-third of the patients and is associated with poor outcome. ALI in SAH may be predisposed by neurogenic pulmonary edema (NPE) and inflammatory mediators. The objective of this study was to assess the immunomodulatory effects of interferon-β (IFN-β) on inflammatory mediators in the lung after experimental SAH.

Methods: Male Wistar rats were subjected to the induction of SAH by means of the endovascular filament method. Sham-animals underwent sham-surgery. Rats received IFN-β for four consecutive days starting at two hours after SAH induction. After seven days, lungs were analyzed for the expression of inflammatory markers.

Results: SAH induced the influx of neutrophils into the lung, and enhanced expression of the pulmonary adhesion molecules E-selectin, inter-cellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 compared to sham-animals. In addition, SAH increased the expression of the chemokines macrophage inflammatory protein (MIP)-1α, MIP-2, and cytokine-induced neutrophil chemoattractant (CINC)-1 in the lung. Finally, tumor necrosis factor-α (TNF-α) was significantly increased in lungs from SAH-animals compared to sham-animals. IFN-β effectively abolished the SAH-induced expression of all pro-inflammatory mediators in the lung.

Conclusions: IFN-β strongly reduces lung inflammation after experimental SAH and may therefore be an effective drug to prevent SAH-mediated lung injury.

Figure 1

SAH was induced in male Wistar rats. Rats were treated with IFN-β for four consecutive days starting at two hours after the induction of SAH. Seven days post-SAH total lung homogenates were prepared and analyzed for inflammatory markers. (a) MPO activity corrected for the amount of protein. (b-d) Expression of endothelial activation markers E-selectin, ICAM-1, and VCAM-1. (e-g) Expression of chemokines MIP-1α, MIP-2, and CINC-1. (h) Expression of TNF-α. (b-h) Data are normalized for the expression of β-actin and GAPDH. Sham: N = 4; Sham/IFN-β: N = 4; SAH: N = 7; SAH/IFN-β: N = 6. *** P < 0.001, ** P < 0.01, * P < 0.05; SAH vs sham or SAH/IFN-β vs SAH. MPO, myeloperoxidase; MIP, macrophage-inflammatory protein; CINC, cytokine-induced neutrophil chemoattractant.