No abstract

Neonatal hypoxia-ischemia (H-I

Objective Inflammation promotes epidermal wound healing but is considered detrimental to recovery from CNS injury. Sick infants have increased levels of cytokines in their CSF that correlate with poor neurological outcome. In this study we investigated the role of neuroinflammation and more specifically, IL-6, in the amplification of subventricular zone (SVZ) and subgranular zone (SGZ) neural precursors after neonatal brain injury. Methods Neonatal hypoxia/ischemia (H/I) was induced in P6 rat pups and IL-6 was quantified with or without Indomethacin administration. Neural precursor responses were evaluated by neurosphere assays as well as by stereological analyses. Studies were performed to determine how IL-6 and LIF affect SVZ cell expansion, proliferation and self-renewal. Results Consistent with earlier studies, SVZ cells expanded after H/I. Contrary to our expectations, Indomethacin significantly decreased both the initial reactive increase in these precursors as well as their ability to self-renew. By contrast, Indomethacin increased proliferation in the SGZ and lateral SVZ. Indomethacin diminished the accumulation of microglia/macrophages and IL-6 production after H/I. In vitro IL-6 enhanced neurosphere growth, self-renewal and tripotentiality and was more effective than LIF in promoting self-renewal. Enhanced precursor self-renewal also was obtained using PGE2, which is downstream of cyclooxygenase-2 and a target of Indomethacin. Interpretation These data implicate neuroinflammation and in particular IL-6 as a positive effector of primitive neural precursor expansion after neonatal brain injury. These findings have important clinical implications, as Indomethacin and other anti-inflammatory agents are administered to premature infants for a variety of reasons.

In this study, we compare the vitreous cytokine profile in patients with proliferative diabetic retinopathy (PDR) to that of patients without PDR. The identification of novel cytokines involved in the pathogenesis of PDR provides candidate therapeutic targets that may stand alone or work synergistically with current therapies in the management of diabetic retinopathy. Undiluted vitreous humor specimens were collected from 74 patients undergoing vitrectomy for various vitreoretinal disorders. Quantitative immunoassay was performed for a panel of 36 neuroinflammatory cytokines in each specimen and assessed to identify differences between PDR (n = 35) and non-PDR (n = 39) patients. Levels of interleukin-8 (IL-8), IL-15, IL-16, vascular endothelial growth factor (VEGF), VEGF-D, c-reactive protein (CRP), serum amyloid-A (SAA), and intracellular adhesion molecule-1 (ICAM1) were significantly increased in the vitreous of PDR patients compared to non-PDR patients (p < 0.05). We report novel increases in IL-15 and IL-16, in addition to the expected VEGF, in the human vitreous humor of patients with PDR. Additionally, we confirm the elevation of ICAM-1, VCAM-1, SAA, IL-8 and CRP in the vitreous of patients with PDR, which has previously been described.