title: Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis.
abstract: Interleukin (IL)-17 plays a critical role in inflammation. Most studies to date have elucidated the inflammatory role of IL-17A, often referred to as IL-17. IL-17F is a member of the IL-17 family bearing 50% homology to IL-17A and can also be present as heterodimer IL-17AF. This study elucidates the distribution and contribution of IL-17A, F and AF in inflammatory arthritis. Neutralizing antibody to IL-17A alone or IL-17F alone or in combination was utilized in the mouse collagen-induced arthritis (CIA) model to elucidate the contribution of each subtype in mediating inflammation. IL-17A, F and AF were all increased during inflammatory arthritis. Neutralization of IL-17A reduced the severity of arthritis, neutralization of IL-17A+IL-17F had the same effect as neutralizing IL-17A, while neutralization of IL-17F had no effect. Moreover, significantly higher levels of IL-17A and IL-17F were detected in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA). IL-17A and AF were detected in synovial fluid mononuclear cells (SFMC) in RA and OA, with IL-17A being significantly higher in RA patients. Enriched CD3(+) T cells from RA PBMCs produced singnificantly high levels of IL-17A and IL-17AF in comparison to OA peripheral blood CD3(+) T cells. IL-17A, F and AF were undetectable in T cells from SFMCs from RA and OA. While IL-17A, F, and AF were all induced during CIA, IL-17A played a dominant role. Furthermore, production of IL-17A, and not IL-17F or IL-17AF, was elevated in PBMCs, SFMCs and enriched peripheral blood CD3(+) T in RA.
authors.affiliation: Section of Rheumatology, Department of Medicine, and the Arizona Arthritis Center, University of Arizona, Tucson, AZ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sarkar
authors.forename: S
authors.initials: S
authors.lastname: Justa
authors.forename: M
authors.initials: M
authors.lastname: Brucks
authors.forename: J
authors.initials: J
authors.lastname: Endres
authors.forename: D A
authors.initials: DA
authors.lastname: Fox
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: F
authors.initials: F
authors.lastname: Alnaimat
authors.forename: B
authors.initials: B
authors.lastname: Whitaker
authors.forename: J C
authors.initials: JC
authors.lastname: Wheeler
authors.forename: B H
authors.initials: BH
authors.lastname: Jones
authors.forename: S R
authors.initials: SR
authors.lastname: Bommireddy
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G; D015850:Interleukin-6; D015851:Interleukin-7; D016179:Granulocyte Colony-Stimulating Factor
keywords: arthritis; cytokine; inflammation