Abstract # 1805 Peripheral cutaneous inflammation induces a brain chemokine response, immune cell infiltration and functional changes

There are now compelling data linking peripheral inflammation and depression. However, the mechanisms that underlie this relationship remain unclear. Using QPCR, we measured brain, lung, liver, skin and peripheral blood leukocyte responses to a well-characterised murine model of psoriasis-like skin inflammation, Aldara (containing the TLR-7 ligand, Imiquimod), in C57BL/6 female mice. We measured tissue responses across a number of time points (4 h, 12 h, 1 d, 3 d and 5 d) and confirmed qPCR findings with protein analysis of brain tissue. Further, we measured behavioural outcomes using burrowing, a rewarding behaviour, deficits in which can be construed as anhedonic. We found significant transcriptional upregulation of a number of chemokines and pro-inflammatory cytokines (including CCL2, CCL5, CXCL10, IL-1B, IL-6 and TNF-a) in the brain and systemic organs and concurrent upregulation of protein was confirmed in the brain. However, the brain response was temporally unique in that the peak transcriptional response was observed at 3 days compared to 12 h to 1 day in the peripheral tissues. Along with chemokine and cytokine induction, we observed the infiltration of immune cells into the brain, including T cells, NK cells and monocytes, particularly at day 3 and day 5. These data indicate that the brain mounts a unique response to peripheral inflammatory stimuli, including chemokine induction that may play a role in immune cell recruitment and subsequent behavioural deficits.