RESUMO
OBJECTIVE: CTLA4-Ig, a biologic agent employed in rheumatoid arthritis (RA) treatment, downregulates the immune response and exerts anti-inflammatory effects acting on different cells including dendritic/T cells interaction and directly on osteoclasts. We investigated the anti-inflammatory effects of CTLA4-Ig in primary monocultures of RA synovial macrophages (SM). METHODS: SM were obtained, from 8 RA patients (7 F, 1 M; DAS28>5.2) who underwent therapeutic arthroscopic synoviectomy and were cultured in the absence and in the presence of CTLA4-Ig at the concentration of [500 microg/ml], the most reliable dose related to the previous pharmacological clinical and experimental experiences. Inflammatory cytokine (IL-6, TNFalpha, IL-1beta) expression was evaluated by immunocytochemistry (ICC with relative image analysis), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: ICC analysis revealed that CTLA4-Ig treatment significantly downregulated cytokine expression (p<0.001 for IL-6, TNFalpha and IL-1beta) when compared to untreated RA SM. WB and qRT-PCR confirmed partially the data. CONCLUSIONS: CTLA4-Ig was found to exert a direct and significant anti-inflammatory effect on primary monocultures of RA SM, suggesting a therapeutic power in different phases of the disease activity.
Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/patologia , Imunoconjugados/farmacologia , Macrófagos/efeitos dos fármacos , Abatacepte , Artrite Reumatoide/cirurgia , Western Blotting , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/imunologia , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas Imunoenzimáticas , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Interleucina-6/biossíntese , Interleucina-6/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Líquido Sinovial/citologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
Tendon adhesions or even secondary ruptures causing severe hand functional impairment still represent a frequent complication after repair of flexor tendon injuries. Secondary treatment of these problems includes tenolysis, one or two stages flexor tendons reconstruction by grafts or even the use of tendon prosthesis. The mechanism and severity of injury, the status of the surrounding tissues and injured finger, the presence of associated lesions, the age of the patient, post-operative management, patient motivation and the surgeon's skill, may all have implications in the final outcome of the tendon reconstruction. A correct evaluation of the problem by means of classifications such as the one described by Boyes, may help the surgeon in choosing the appropriate technique.