A novel platform for in vivo detection of cytokine release within discrete brain regions

Mounting evidence indicates that cytokines secreted by innate immune cells in the brain play a central role in regulating neural circuits that subserve mood, cognition, and sickness responses. A major impediment to the study of neuroimmune signaling in healthy and disease states is the absence of tools for in vivo detection of cytokine release in the brain. Here we describe the design and application of a cytokine detection device capable of serial monitoring of local cytokine release in discrete brain regions. The immunocapture device consisted of a modified optical fiber labeled with a capture antibody specific for the pro-inflammatory cytokine interleukin-1 beta (IL-1β). Using a sandwich immunoassay method, in vitro data demonstrate that the sensing interface of the modified optical fiber has a linear detection range of 3.9 pg mL−1-500 pg mL−1 and spatial resolution on the order of 200-450 μm. Finally, we show that the immunocapture device can be introduced into a perforated guide cannula for repeated analyte measurements in vivo. An increase in fluorescence detection of spatially localized intrahippocampal IL-1β release was observed following a peripheral lipopolysaccharide challenge in Sprague-Dawley rats. This novel immunosensing technology represents an opportunity for unlocking the function of neuroimmune signaling.