Antibodies to complement receptor 3 treat established inflammation in murine models of colitis and a novel model of psoriasiform dermatitis.
Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic administration of anti-CR3 significantly ameliorated established intestinal inflammation following the intrarectal administration of trinitrobenzene sulfonic acid (TNBS-colitis), as well as colitis and skin inflammation in C57BL/10 RAG-2(-/-) mice reconstituted with CD4+CD45RBhigh T cells. The hyperproliferative skin inflammation in this novel murine model demonstrated many characteristics of human psoriasis, and was prevented by the adoptive transfer of CD45RBlow T cells. In vitro and in vivo studies suggest that anti-CR3 treatment may act, at least in part, by directly inhibiting IL-12 production by APCs. Administration of anti-CR3 may be a useful therapeutic approach to consider for the treatment of inflammatory bowel disease and psoriasis in humans.
Leon
Francisco
F
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA.
Contractor
Nikhat
N
Fuss
Ivan
I
Marth
Thomas
T
Lahey
Edward
E
Iwaki
Shoko
S
la Sala
Andrea
A
Hoffmann
Victoria
V
Strober
Warren
W
Kelsall
Brian L
BL
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D003872:Dermatitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D011565:Psoriasis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D000906:Antibodies; D018836:Inflammation Mediators; D016177:Macrophage-1 Antigen; D014302:Trinitrobenzenesulfonic Acid