Interleukin-1β Increases Release of Endothelin-1 and Tumor Necrosis Factor as Well as Reactive Oxygen Species by Peripheral Leukocytes During Experimental Subarachnoid Hemorrhage

Magdalena      Larysz-Brysz; Joanna      Lewin-Kowalik; Zenon      Czuba; Katarzyna      Kotulska; Edyta      Olakowska; Wieslaw      Marcol; Arkadiusz      Liskiewicz; Halina      Jedrzejowska-Szypulka

doi:10.2174/156720212801619045

Abstract

In the subarachnoid hemorrhage (SAH) blood mixes with cerebrospinal fluid, what starts immunoinflammatory processes - increased synthesis of proinflammatory cytokines, and formation of reactive oxygen species (ROS), resulting in pre-activation of different populations of peripheral leukocytes. Migration of leukocytes to the brain parenchyma through broken blood brain barrier may produce extra brain tissue injury besides of that resulting from SAH.

We examined in adult rats the effect of interleukin-1β (IL-1β) neutralization on secretion of cytokines as well as production of ROS in the course of SAH.

SAH was produced by injection of 150 μL of autologous arterial blood into cisterna magna. In 50% of animals, IL-1beta activity was inhibited by intracerebroventricular administration of anti-rat IL-1β antibodies. Ninety minutes or 24 hrs following surgery, blood samples were drawn from the extraorbital plexus and centrifuged to obtain two leukocyte subpopulations – polymorphonuclear (PMN) and mononuclear (MN). The chemiluminescence, a hallmark of ROS synthesis, was measured in PMNs. In supernatants from MNs cultures, concentrations endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed.

SAH caused the increase ofn PMNs chemiluminescence as well as the increase of production of ET-1 and TNF-α by MNs but had no influence on IL-6 concentration. Neutralization of IL-1β resulted in significant decrease of chemiluminescence as well as concentration of both ET-1 and TNF-α, while IL-6 concentration was increased.

These revealed an important role of IL-1β in the activation of peripheral leukocytes in the course of subarachnoid hemorrhage.

Keywords: Chemiluminescence, cytokines, interleukin-1β, mononuclear leukocytes, neutrophils, reactive oxygen species (ROS), subarachnoid hemorrhage, proinflammatory, leukocytes, IL-1beta, cytokines, intracerebroventricular, polymorphonuclear , interleukin, ET-1 , TNF-α