The interrelated roles of TGF-beta and IL-10 in the regulation of experimental colitis.

Abstract

In the present study, we define the relation between TGF-beta and IL-10 in the regulation of the Th1-mediated inflammation occurring in trinitrobenzene sulfonic acid (TNBS)-colitis. In initial studies, we showed that the feeding of trinitrophenol-haptenated colonic protein to SJL/J mice induces CD4(+) regulatory T cells that transfer protection from induction of TNBS-colitis, and that such protection correlates with cells producing TGF-beta, not IL-10. Further studies in which SJL/J mice were fed haptenated colonic protein, and then administered either anti-TGF-beta or anti-IL-10 at the time of subsequent TNBS administration per rectum, showed that while both Abs abolished protection, anti-TGF-beta administration prevented TGF-beta secretion, but left IL-10 secretion intact; whereas anti-IL-10 administration prevented both TGF-beta secretion and IL-10 secretion. Thus, it appeared that the protective effect of IL-10 was an indirect consequence of its effect on TGF-beta secretion. To establish this point further, we conducted adoptive transfer studies and showed that anti-IL-10 administration had no effect on induction of TGF-beta producing T cells in donor mice. However, it did inhibit their subsequent expansion in recipient mice, probably by regulating the magnitude of the Th1 T cell response which would otherwise inhibit the TGF-beta response. Therefore, these studies suggest that TGF-beta production is a primary mechanism of counter-regulation of Th1 T cell-mediated mucosal inflammation, and that IL-10 is necessary as a secondary factor that facilitates TGF-beta production.

• Authors: Ivan J Fuss, Monica Boirivant, Brian Lacy, Warren Strober
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 2 Pg. 900-8 (Jan 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 11777988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Monoclonal
• Haptens
• Picrates
• Transforming Growth Factor beta
• Interleukin-10
• Trinitrobenzenesulfonic Acid
• picric acid

Topics

• Adjuvants, Immunologic (biosynthesis, physiology)
• Administration, Oral
• Administration, Rectal
• Adoptive Transfer
• Animals
• Antibodies, Monoclonal (administration & dosage)
• CD4-Positive T-Lymphocytes (immunology)
• Colitis (chemically induced, etiology, immunology, prevention & control)
• Colon (immunology, metabolism)
• Down-Regulation (immunology)
• Haptens (administration & dosage)
• Interleukin-10 (immunology, physiology)
• Lymphocyte Activation (immunology)
• Male
• Mice
• Mice, Inbred Strains
• Picrates (administration & dosage)
• T-Lymphocyte Subsets (immunology, transplantation)
• Transforming Growth Factor beta (biosynthesis, immunology, physiology)
• Trinitrobenzenesulfonic Acid (administration & dosage)