Brain IL-1β Increases Neutrophil and Decreases Lymphocyte Counts through Stimulation of Neuroimmune Pathways

Abstract

Leukocytosis after cerebral injury is well described and may participate in the generation of cerebral damage. However, the mechanisms of brain-induced leukocytosis are still speculative. Since it is known that proinflammatory cytokines are involved in neuroimmunomodulation and since others and we have demonstrated high cytokine levels in the cerebrospinal fluid following injury, we supposed that brain cytokines may also influence leukocyte counts. In order to evaluate this hypothesis, we established an animal model using continuous intracerebroventricular (icv), intrahypothalamic (ih), or intravenous infusion of the proinflammatory cytokines tumor necrosis factor (TNF)-α and IL-1β. Controls received vehicle solution. With this experimental paradigm we could show that icv and ih infusion of IL-1β but not TNF-α dramatically increased neutrophil counts, whereas lymphocytes dropped. Blocking the hypothalamic–pituitary–adrenal (HPA) axis by hypophysectomy abolished the neutrophilia, whereas the lymphopenia remained unchanged. Furthermore, application of the β2-adrenoreceptor antagonist propranolol prevented the decrease of lymphocytes and diminished the neutrophilia. All parameters normalized within 48 h after termination of infusion. So, our results demonstrate that brain IL-1β can modify blood leukocyte counts through stimulation of both the sympathetic nervous system (SNS) and the HPA axis.