RESUMEN
This is a review concerning the role of interleukin-17, a proinflammatory cytokine, produced by activated memory CD4+ T cells, in pathogenesis of rheumatoid arthritis. As interleukin-17 shares properties with IL-1 and TNF-alpha, it may induce joint inflammation and bone and cartilage destruction. This cytokine is found in synovial fluids of patients with rheumatoid arthritis, and produced by rheumatoid arthritis synovium. It increases IL-6 production, induces collagen degradation and decreases collagen synthesis by synovium and cartilage and proteoglycan synthesis in cartilage. Interleukin-17 is also able to increase bone destruction and reduce its formation. Blocking of interleukin-17 with specific inhibitors provides a protective inhibition of cartilage and bone degradation.
Asunto(s)
Artritis Reumatoide/etiología , Interleucina-17/fisiología , Animales , Artritis Reumatoide/patología , Artritis Reumatoide/fisiopatología , Cartílago Articular/metabolismo , Cartílago Articular/patología , Células Cultivadas , Colágeno/biosíntesis , Colágeno/metabolismo , Expresión Génica , Humanos , Interleucina-1/fisiología , Interleucina-17/análisis , Interleucina-17/antagonistas & inhibidores , Interleucina-17/biosíntesis , Interleucina-17/genética , Ratones , Osteoblastos/citología , Osteoblastos/patología , Proteoglicanos/metabolismo , Líquido Sinovial/química , Membrana Sinovial/metabolismo , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
Synthesis and evaluation of anti-inflammatory activity in rats with adjuvant arthritis of aryl sulfonyl derivatives of nonproteinogenic aromatic amino acids is reported. The studied compounds were synthesized by introducing residues of benzene-, p-toluene-, and p-bromobenzene sulfonic acids into threo-DL-phenylserine and erythro-DL-p-nitrophenylserine structures. From the set of 12 compounds tested in animal screening, N-(p-bromobenzenesulfonyl)-erythro-DL-p-nitrophenylserine ethyl ester 12 demonstrated the most pronounced anti-inflammatory activity. This compound inhibited inflammation process in polyarthritis phase by 53% (P < 0.001) though it was slightly toxic (LD50 > 6,000 mg kg(-1) for mice).