Interferon-β attenuates lung inflammation following experimental subarachnoid hemorrhage

Abstract

IntroductionAneurysmal 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.MethodsMale 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.ResultsSAH 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.ConclusionsIFN-β strongly reduces lung inflammation after experimental SAH and may therefore be an effective drug to prevent SAH-mediated lung injury.

Isobavachalcone attenuates lipopolysaccharide-induced ICAM-1 expression in brain endothelial cells through blockade of toll-like receptor 4 signaling pathways

“…IFN-β induction during TLR3 signaling was hypothesized to be a critical component of limiting forces to immunopathologic damage (Hooks et al, 2008). Indeed, IFN-β has been reported to decrease the expression of adhesion molecules on endothelial cells (Cobelens et al, 2010;Billiau et al, 2004), monocytes (de Paus et al, 2013) and retinal pigment epithelial cells (Hooks et al, 2008) and to reduce the migration of inflammatory cells across the blood-brain barrier (Veldhuis et al, 2003;Billiau et al, 2004). In this context, it is plausible that the reduction of IFN-β expression at high doses of isobavachalcone might contribute to the loss of its inhibitory effect on NF-κB activity and ICAM-1 expression, whereas enough IFN-β might be available at low dose treatments to suppress inflammatory responses in cerebral endothelial cells stimulated with poly[I:C].…”

S100B Induces the Release of Pro-Inflammatory Cytokines in Alveolar Type I-like Cells

“…Moreover, S IOOB did not stimulate AT-Ilike cells to secrete other inflammatory mediators involved in ALI and NPE pathogenesis, such as sICAM-I, CINC-I and CINC-3 (25). One may suppose that these mediators are induced by releasing factors other than S100B orland are produced by cellular types other than AT-I cells.…”

Respiratory mechanics in brain injury: A review

“…In fact, an upregulation of the soluble intercellular adhesion molecule1 (ICAM1) was found in the lungs of BD animals [29] . Similarly, Cobelens et al [31] found that experimental subarachnoid hemorrhage was associated with neutrophil influx into the lungs as well as increased expression of pulmonary adhesion molecules and chemokines. Adhesion molecules through activation, firm adhesion, and the chemotactic migration of leukocytes [32] may contribute to lung injury.…”