Interleukin-4 Programmed Macrophages Suppress Colitis and Do Not Enhance Infectious-Colitis, Inflammation-Associated Colon Cancer or Airway Hypersensitivity

Frontiers in Immunology, Vol. 12 (2021)

Keywords
Authors
  • Blanca E. Callejas
  • Gastrointestinal Research Group, Inflammation Research Network and Host-Parasite Interaction Group, Department of Physiology and Pharmacology, Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  • Graham A. D. Blyth
  • Department of Microbiology, Immunology and Infectious Disease, Cumming School of Medicine, University of Calgary and Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
  • Nicholas Jendzjowsky
  • Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  • Arthur Wang
  • Gastrointestinal Research Group, Inflammation Research Network and Host-Parasite Interaction Group, Department of Physiology and Pharmacology, Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  • Anshu Babbar
  • Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
  • Konstantin Koro
  • Department of Pathology and Laboratory Medicine, Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  • Richard J. A. Wilson
  • Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  • Margaret M. Kelly
  • Department of Pathology and Laboratory Medicine, Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  • Margaret M. Kelly
  • Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  • Eduardo R. Cobo
  • Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
  • Derek M. McKay
  • Gastrointestinal Research Group, Inflammation Research Network and Host-Parasite Interaction Group, Department of Physiology and Pharmacology, Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

Abstract

The murine interleukin-4 treated macrophage (MIL4) exerts anti-inflammatory and pro-healing effects and has been shown to reduce the severity of chemical-induced colitis. Positing M(IL4) transfer as an anti-inflammatory therapy, the possibility of side-effects must be considered. Consequently, bone marrow-derived M(IL4)s were administered via intraperitoneal injection to mice concomitant with Citrobacter rodentium infection (infections colitis), azoxymethane/dextran sodium sulphate (AOM/DSS) treatment [a model of colorectal cancer (CRC)], or ovalbumin sensitization (airway inflammation). The impact of M(IL4) treatment on C. rodentium infectivity, colon histopathology, tumor number and size and tissue-specific inflammation was examined in these models. The anti-colitic effect of the M(IL4)s were confirmed in the di-nitrobenzene sulphonic acid model of colitis and the lumen-to-blood movement of 4kDa FITC-dextran and bacterial translocation to the spleen and liver was also improved by M(IL4) treatment. Analysis of the other models of disease, that represent comorbidities that can occur in human inflammatory bowel disease (IBD), revealed that M(IL4) treatment did not exaggerate the severity of any of the conditions. Rather, there was reduction in the size (but not number) of polyps in the colon of AOM/DSS-mice and reduced infectivity and inflammation in C. rodentium-infected mice in M(IL4)-treated mice. Thus, while any new therapy can have unforeseen side effects, our data confirm and extend the anti-colitic capacity of murine M(IL4)s and indicate that systemic delivery of one million M(IL4)s did not exaggerate disease in models of colonic or airways inflammation or colonic tumorigenesis.

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