RESUMEN
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.
Asunto(s)
Artritis Experimental/inmunología , Artritis Experimental/metabolismo , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Interleucina-7/inmunología , Interleucina-7/metabolismo , Animales , Anticuerpos/sangre , Anticuerpos/inmunología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Interleucina-6/sangre , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Ratones , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
There is a high prevalence of hepatitis C virus (HCV) infection among immunosuppressed patients including renal transplant recipients. The study investigated serum viral loads for up to 6 months posttransplantation among these patients. Serum viral load was serially monitored using real-time polymerase chain reaction (PCR) in 25 HCV-positive renal transplant recipients pretransplantation as well as day 10 and 6 months posttransplantation. A liver biopsy specimen obtained under vision at the time of transplantation was analyzed for viral load as well as for histological changes. There was increased viremia at day 10 followed by a significant (2 log) reduction at 6 months posttransplantation. Pretransplantation serum and intrahepatic viral load showed significant positive correlations (r = 0.727; P = .001), the latter also reflecting liver fibrosis score (r = 0.423; P = .05). The findings suggested that serum viral load reflects intrahepatic viral load, which in turn correlates with liver fibrosis. At 6 months posttransplantation, the modulatory effects of immunosuppressive drugs and of the host immune response may lead to a reduced viral load.