Intra-colonic administration of the TLR7 agonist R-848 induces an acute local and systemic inflammation in mice.

Abstract

Imidazoquinoline compounds, such as resiquimod (R-848), are well known topically active immune modifiers that bind to toll-like receptor 7 (TLR7). The aim of this study was to characterize the R-848 induced inflammatory response in mice and to validate the response using methyl-prednisolone and anti-TNF antibody. Intra-colonic application of R-848 to BALB/c mice induced a systemic transient elevation of TNF, CXCL1, IL-6, and IL-12p40 and a colonic elevation of cytokines/chemokines and iNOS, without infiltration of immune cells or epithelial destruction. Treatment with methyl-prednisolone or anti-TNF antibody attenuated the systemic (TNF, IL-6, IL-12p40, and CXCL1) and local (colonic TNF and iNOS mRNA expression) response induced by R-848. In summary, intra-colonic administration of R-848 induces an acute systemic and local inflammatory response, which can be attenuated by steroids or anti-TNF antibody. We suggest that the R-848 inflammatory model can be useful in future validation of new drugs for gastrointestinal inflammatory conditions.

• Authors: Agneta Karlsson, Ke Jägervall, Helena Utkovic, Lisa Karlsson, Erika Rehnström, Maria Fritsch Fredin, Per-Göran Gillberg, Liselotte Jansson, Erik Michaëlsson, Silvia Melgar
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 367 Issue 2 Pg. 242-8 (Mar 07 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18083110 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Imidazoles
• Immunologic Factors
• Membrane Glycoproteins
• Tlr7 protein, mouse
• Toll-Like Receptor 7
• resiquimod

Topics

• Animals
• Colon (drug effects, immunology)
• Cytokines (immunology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Imidazoles (administration & dosage)
• Immunity, Innate (drug effects, immunology)
• Immunologic Factors (immunology)
• Inflammation (chemically induced, immunology, pathology)
• Membrane Glycoproteins (antagonists & inhibitors)
• Mice
• Mice, Inbred BALB C
• Toll-Like Receptor 7 (antagonists & inhibitors)