Affiliation:
1. Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
2. Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Abstract
Objectives The purpose of the present study was to investigate whether intramuscular BoNT/A injections cause an systemic inflammatory response and a local inflammatory response in the muscle tissue. Methods Thirty-two male Sprague Dawley rats treated with BoNT/A (i.m., 1IU) were divided in four groups, depending on the time of BoNT/A injection (2 days before, 1, 2, and 4 weeks before the experiment). Bio-Plex Pro Rat Cytokine 23-plex Multiplex Assay (Bio-Rad, USA). Results Systemic inflammation: 17 cytokines (IL1-α ( p = 0.005), IL-1β ( p = 0.01), IL-2 ( p = 0.04), IL-4 ( p = 0.03), IL-6 ( p = 0.03), IL-10 ( p = 0.02), IL12(p70) ( p = 0.03), IL-13 ( p = 0.04), IL-17 ( p = 0.03), GM-CSF ( p = 0.03), INF-γ ( p = 0.03), MIP-1α ( p = 0.03), MIP-3α ( p = 0.04), RANTES ( p = 0.001), TNF-α ( p = 0.04), vascular endothelial growth factor ( p = 0.03), and MCP-1 ( p = 0.02)) showed significantly higher expression levels 2 days after intramuscular BoNT/A injections compared to other time points (1, 2, and 4 weeks). Local inflammation: 12 cytokines (IL-1β ( p = 0.02), IL-6 ( p = 0.002), IL-10 ( p = 0.02), IL-13 ( p = 0.04), IL-17 ( p = 0.02), TNF-α ( p = 0.001), GM-CSF ( p = 0.01), M-CSF ( p = 0.04), MIP-1α ( p = 0.04), MIP-3α ( p = 0.002), RANTES ( p = 0.02), and MCP-1( p = 0.004)) showed higher expression levels 2 and/or 4 weeks after intramuscular BoNT/A injections compared to the other time points (2 days and 1 week). Conclusion Intramuscular BoNT/A injections result in a rapid systemic inflammatory response that only lasts a couple of days. At the same time, intramuscular BoNT/A injections cause an inflammatory response locally in the muscle with significantly higher cytokine levels 2 and/or 4 weeks after injections.