E-Mail karger@karger.com Original Paper Neuroimmunomodulation 2016;23:81–87 DOI: 10.1159/000444529 Intravitreous Injection of Interleukin-6 Leads to a Sprouting in the Retinotectal Pathway at Different Stages of Development Grasielle D. Menezes Vanessa G. Goulart Sheila Espírito-Santo Priscilla Oliveira-Silva Claudio Alberto Serfaty Paula Campello-Costa Programa de Neurociências, Departamento de Neurobiologia, Universidade Federal Fluminense, Niterói, Brazil Introduction Interleukin-6 (IL-6) belongs to the neuropoietic cyto- kine family that is present in the central nervous system, playing a large variety of functions [1, 2]. This interleukin increases the survival of retinal ganglion cells (RGCs) in culture [3–5] and also in an in vivo model of elevated ocular pressure [6, 7]. Other studies have associated IL-6 to synaptic plasticity since endogenous IL-6 inhibition can prolong long-term potentiation and improve memo- ry [8–11]. Also, IL-6 modulates both excitatory and in- hibitory synapses and reduces paired-pulse inhibition [12]. IL-6 also has an effect upon dendritic spine mor- phology, leading to the formation of new synaptic con- tacts [12]. Recent studies have indicated a relationship between increased levels of IL-6 and developmental dis- eases with impaired synapse and dendritic spine forma- tion or elimination [13–15]. Indeed, both the behavior and brain morphological alterations observed in autism are blocked by anti-IL-6 antibody [16]. Therefore, IL-6 might be a key component for the development of synap- tic contacts and changes in its levels might be sufficient to impair the correct brain connectivity. The retinotectal pathway is a useful model to study the development of central connections and the mechanisms underlying this process. It is formed by RGC axons that innervate the superior colliculus (SC) [17]. At birth, fibers from both eyes diffusely innervate the entire SC and, dur- Key Words Interleukin-6 · Central nervous system · Retinotectal projections · Plasticity Abstract Objective: The development of retinotectal pathways form precise topographical maps is usually completed by the third postnatal week. Cytokines participate in the develop- ment and plasticity of the nervous system. We have previ- ously shown that in vivo treatment with interleukin 2 dis- rupts the retinocollicular topographical order in early stages of development. Therefore, we decided to study the effect of a single intravitreous injection of IL-6 upon retinotectal circuitry in neonates and juvenile rats. Materials and Meth- ods: Lister Hooded rats received an intravitreous injection of IL-6 (50 ng/ml) or vehicle (PBS) at either postnatal day (PND)10 or PND30 and the ipsilateral retinotectal pathway was evaluated 4 or 8 days later, respectively. Results: Our data showed that, at different stages of development, a single IL-6 intravitreous treatment did not produce an inflammatory re- sponse and increased retinal axon innervation throughout the visual layers of the superior colliculus. Conclusions: Taken together, our data provide the first evidence that a single in- travitreous injection with IL-6 leads to sprouting in the sub- cortical visual connections and suggest that small changes in IL-6 levels might be sufficient to impair the correct neuronal circuitry fine-tuning during brain development. © 2016 S. Karger AG, Basel Received: September 17, 2015 Accepted after revision: February 5, 2016 Published online: April 1, 2016 Paula Campello-Costa, PhD Programa de Neurociências, Instituto de Neurobiologia Universidade Federal Fluminense Caixa Postal 100180, Niterói, RJ 24001-970 (Brazil) E-Mail paula.campello  @  pq.cnpq.br © 2016 S. Karger AG, Basel 1021–7401/16/0232–0081$39.50/0 www.karger.com/nim