Unexpected Macrophage Activity Alters the Inflammatory Process in Necrotizing Enterocolitis
Jessica L. Raque1,2*, Paul J. Matheson1,2, Kevin Connolly1,2, Jessica A. Shepherd1,2, Eric A. Stamper1,2, Kelly M. McMasters1,2, Victoria Graham1,2, R. Neal Garrison1,2, Jason W. Smith1,2, Cynthia D. Downard1,2 and Hiram C. Polk Jr1,2
- *Corresponding Author:
- Jessica L. Raque
Department of Surgery, School of Medicine
University of Louisville, Louisville, KY 40202, USA
E-mail: [email protected]
Received date: May 13, 2017; Accepted date: May 31, 2017; Published date: June 06, 2017
Citation: Raque JL, Matheson PJ, Connolly K, Shepherd JA, Stamper EA, et al. (2017) Unexpected Macrophage Activity Alters the Inflammatory Process in Necrotizing Enterocolitis. J Cytokine Biol 2:115.
Copyright: © 2017 Raque Jl, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Macrophages play a role in clearing bacteria from the gut in the initial stages of necrotizing enterocolitis (NEC). Macrophage Inflammatory Protein-1α (MIP-1α), also known as CCL3, is a chemokine produced by macrophages that enhances the immune response. It acts as both a recruiter of immune cells and a coactivator of other macrophages. Interleukin-12 (IL-12) is a pro-inflammatory chemotactant produced by several types of phagocytic cells such as dendritic cells and neutrophils, but primarily by macrophages. We hypothesized that the pro-inflammatory state associated with NEC pathophysiology would induce increased expression of MIP-1α and IL-12 that would be detectable in serum and intestinal tissue.
Methods: Timed pregnant Sprague-Dawley rats were randomized by litter. Controls were delivered vaginally and dam-fed. NEC pup groups were delivered 12 h prematurely via Cesarean section, formula fed, given a single oral dose of lipopolysaccharide, and subjected to intermittent cold and hypoxia as part of a proven NEC rat model protocol. Animals were sacrificed at 0, 12, 24, 48, 72, and 96 h of life and serum and intestinal tissue samples were collected. Samples were analysed via western blot using antibodies with affinity to MIP-1α and IL-12 respectively.
Results: Serum and ileal levels of MIP-1 alpha were increased from 48 to 72 h in NEC animals when compared with controls. Serum and ileal IL-12 was downregulated in NEC groups at 12 and 24 h compared to controls.
Conclusion: Macrophage function plays an important role in the first 48 h of NEC pathophysiology. Downregulation of IL-12 in the setting of increased MIP-1α expression may represent deranged or inhibited macrophage function in the context of NEC pathogenesis. Further work to elucidate the significance of these findings is warranted.