title: Treatment of collagen-induced arthritis by Natura-alpha via regulation of Th-1/Th-17 responses.
abstract: Cytokines and CD4(+) Th cells play a crucial role in the pathogenesis of rheumatoid arthritis. Among the Th populations, Th-1 and Th-17 have been described as pathogenic in collagen-induced arthritis (CIA) whereas Th-2 and Treg were found to have protective effects. The objective of this study was to examine the affect of Natura-alpha, a newly developed cytokine regulator, on CIA and on Th cell development. Natura-alpha treatment was administered before or during arthritis induction. Anti-type II collagen antibodies and cytokine expression were evaluated by ELISA. Emergence of CD4(+)CD25(+)Foxp3(+) T cells was assessed by flow cytometry. Th-17 differentiation of naive CD4 T cells was assessed in cultures with anti-CD3 and anti-CD28. We showed that Natura-alpha both prevented and treated CIA. We further demonstrated that in vivo treatment with Natura-alpha inhibited IL-17 production and anti-type II collagen IgG development. We showed in vitro, using an APC-free system, that Natura-alpha acted directly on differentiating T cells and inhibiting the formation of Th-1 and Th-17 cells but did not affect Th-2 cells. Since Natura-alpha inhibits a large spectrum of important pathogenic factors in CIA, it may provide a new and powerful approach to the treatment of rheumatoid arthritis and other inflammatory diseases.
authors.affiliation: Institut Cochin, Université Paris Descartes CNRS (UMR 8104), Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Glatigny
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Blaton
authors.forename: Simon K
authors.initials: SK
authors.lastname: Mencher
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mistou
authors.forename: Bruno
authors.initials: B
authors.lastname: Lucas
authors.forename: Catherine
authors.initials: C
authors.lastname: Fournier
authors.forename: Long G
authors.initials: LG
authors.lastname: Wang
authors.forename: Gilles
authors.initials: G
authors.lastname: Chiocchia
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood / Q000378:metabolism; D053759:Interleukin-23 / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000906:Antibodies; D024043:Collagen Type II; D007074:Immunoglobulin G; D007211:Indoles; D020381:Interleukin-17; D053759:Interleukin-23; C547344:N-methyl-delta-3,3-dihydroindole-2,2 diketone; D007371:Interferon-gamma