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Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens

1
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, Saint Paul, MN 55108-6010, USA
2
Department of Science, Concordia University, 1282 Concordia Avenue, Saint Paul, MN 55104-5494, USA
*
Author to whom correspondence should be addressed.
Pathogens 2014, 3(2), 249-257; https://doi.org/10.3390/pathogens3020249
Received: 26 November 2013 / Revised: 17 March 2014 / Accepted: 20 March 2014 / Published: 2 April 2014
(This article belongs to the Special Issue Gut Microbiome)
Epithelial cells represent the first line of host immune defense at mucosal surfaces. Although opioids appear to increase host susceptibility to infection, no studies have examined opioid effects on epithelial immune functions. We tested the hypothesis that morphine alters vectorial cytokine secretion from intestinal epithelial cell (IPEC-J2) monolayers in response to enteropathogens. Both entero-adherent Escherichia coli O157:H7 and entero-invasive Salmonella enterica serovar Typhimurium increased apically-directed IL-6 secretion and bi-directional IL-8 secretion from epithelial monolayers, but only IL-6 secretion evoked by E. coli was reduced by morphine acting through a naloxone-sensitive mechanism. Moreover, the respective type 4 and 5 Toll-like receptor agonists, lipopolysaccharide and flagellin, increased IL-8 secretion from monolayers, which was also attenuated by morphine pretreatment. These results suggest that morphine decreases cytokine secretion and potentially phagocyte migration and activation directed towards the mucosal surface; actions that could increase host susceptibility to some enteric infections. View Full-Text
Keywords: morphine; opioid receptors; small intestine; epithelial cell; Escherichia coli; Salmonella enterica; interleukin-6; interleukin-8; Toll-like receptors; swine morphine; opioid receptors; small intestine; epithelial cell; Escherichia coli; Salmonella enterica; interleukin-6; interleukin-8; Toll-like receptors; swine
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Brosnahan, A.J.; Jones, B.J.; Dvorak, C.M.; Brown, D.R. Morphine Attenuates Apically-Directed Cytokine Secretion from Intestinal Epithelial Cells in Response to Enteric Pathogens. Pathogens 2014, 3, 249-257.

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