ABSTRACT
BACKGROUND/AIMS: This study was undertaken to identify the intracellular signaling pathway involved in induction of macrophage migration inhibitory factor (MIF) in human rheumatoid arthritis (RA) synovial fibroblasts. METHODS: Human RA synovial fibroblasts were treated with concanavalin A (ConA), various cytokines, and inhibitors of signal transduction molecules. The production of MIF by synovial fibroblasts was measured in culture supernatants by ELISA. The expression of MIF mRNA was determined using reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Phosphorylation of p38 mitogen-activated protein (MAP) kinase in synovial fibroblasts was confirmed using Western blotting. The expression of MIF and p38 MAP kinase in RA synovium was determined using dual immunohistochemistry. RESULTS: The production of MIF by RA synovial fibroblasts increased in a dose-dependent manner after ConA stimulation. MIF was also induced by interferon-gamma, CD40 ligand, interleukin-15, interleukin-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta. The production of MIF by RA synovial fibroblasts was significantly reduced after inhibition of p38 MAP kinase. The expression of MIF and p38 MAP kinase was upregulated in the RA synovium compared with the osteoarthritis synovium. CONCLUSIONS: These results suggest that MIF production was induced through a p38 MAP-kinase-dependent pathway in RA synovial fibroblasts.
Subject(s)
Humans , Arthritis, Rheumatoid/genetics , Base Sequence , Cells, Cultured , Concanavalin A/pharmacology , Cytokines/pharmacology , DNA Primers/genetics , Fibroblasts/drug effects , Macrophage Migration-Inhibitory Factors/biosynthesis , RNA, Messenger/genetics , Signal Transduction/drug effects , Synovial Membrane/drug effects , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
BACKGROUND & OBJECTIVE: Intraarticular (i.a) drug application is consider to be a new therapeutic approach for the treatment of postoperative pain after arthroscopic knee surgery without any systemic adverse effects. Lornoxicam, a nonsteroid anti-inflammatory drug is a short acting agent, and its anti-inflammatory and analgesic activity may be effective in the postoperative pain management in minor surgery. In this study, the effects of intraarticular administration of lornoxicam on the synovium and articular cartilage in the rat knee joint were investigated. METHODS: Lornoxicam (0.25 ml) was given as an injection into the right knee joint and 0.25 ml of 0.9 per cent saline solution by injection into the left knee joint as a control in 25 rats. Groups of five rats were sacrificed by a lethal injection of ketamine 1st, 2nd, 7th, 14th and 21st days after lornoxicam administration. Knee joints were detached, fixed in 10 per cent buffered formalin and decalcified. Serial sections of 5 microm were stained with haematoxylin-eosin and evaluated for the presence of inflammation in the articular, periarticular regions and synovium. Inflammatory changes in the joints were graded according to a five-point scale, histologically. RESULTS: There were no significant differences in inflammation and cartilage degeneration, between control and lornoxicam applied knees. Grade 3 inflammatory changes occurred only in one knee in lornoxicam group, at 24 h after injection. No pathological changes were observed in both groups at any time point. INTERPRETATION & CONCLUSION: Lornoxicam did not show significant effect on inflammation on rat synovia in knee joint. Further studies including in human need to be done before any recommendations are made for i.a. administration of lornoxicam.
Subject(s)
Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cartilage, Articular/drug effects , Injections, Intra-Articular , Knee Joint/drug effects , Pain, Postoperative/drug therapy , Piroxicam/analogs & derivatives , Rats , Rats, Sprague-Dawley , Synovial Membrane/drug effectsABSTRACT
To evaluate the histological and ultrastructural alterations in rabbit knee joint cartilage and synovia induced by intraarticular injections of 2 water soluble contrast agents. The study was conducted at the Department of Orthopedics and Traumatology, Medical Faculty, Osmangazi University, Eskisehir, Turkey in January 2002. To examine the effect of contrast agents on articular cartilage and synovial membrane, rabbit model was used. Specimens from 62 knee joints were examined by light microscopy and transmission electron microscopy one hour, one day, one week and 2 weeks after intraarticular administration of gadolinium-diethylenetriamine pentaacetic acid, iopromide or saline. In the knees injected with saline, light microscopic changes of the synovium consisted of edema only. Edema and hyperemia were seen in contrast agent injected knees. Ultrastructurally, numerous and large pinocytotic vesicles in A cells of the synovial membrane were seen in contrast agent injected groups. In the knees injected with saline the cartilage were ultrastructurally normal but contrast agent injected knees showed increased activation of chondrocytes with increase of dense glycogen accumulation, large lipid vacuoles and matrix material. There were very rare pycnotic cells in these samples. The rating scale has been used and the means of the total scores were determined for the groups. The effects of contrast agents reduced gradually on the cartilage and synovium in general but did not become completely normal in the observation period
Subject(s)
Animals , Cartilage, Articular/drug effects , Synovial Membrane/drug effects , Injections, Intra-Articular , Contrast Media/administration & dosage , Gadolinium DTPA/adverse effects , Iohexol/adverse effects , RabbitsABSTRACT
La aplicación juiciosa de esteroides intra y periarticulares para padecimientos reumáticos y de tejidos blandos, se justifica debido a que dentro de la fisiopatogenia de estas enfermedades se encuentra la inflamación crónica de sinoviales, tendones y otros tejidos adyacentes. Cada esteroides de depósito existente guarda ventajas intrínsecas. El dominio del procedimiento de infiltración favorece la no ocurrencia de complicaciones. Nosotros efectuamos un estudio de retrocohorte de todos los pacientes que han requerido la aplicación de corticoides en forma de infiltración en los últimos dos años en nuestro servicio. El total de enfermos fue de 578. El 43 por ciento (250) correspondió a AR; 170 a OA (29 por ciento); reumatismos extrarticulares 98 casos (17 por ciento). El resto fueron espondiloartropatías (5 por ciento) y ARJ, 30 (5 por ciento). No encontramos complicaciones infecciosas y sí hubo atrofia de piel en 9 casos de reumatismos extrarticulares
Subject(s)
Synovial Membrane/drug effects , Adrenal Cortex Hormones/therapeutic use , Chronic Disease/rehabilitation , Rheumatic Diseases/therapyABSTRACT
The target cellular response to glucocorticoids is proportional to the concentration or affinity of specific receptors to these substances. To look for a correlation between glucocorticoid receptors concentrations in synovial wall cells and the clinical response to steroidal treatment in patients with rheumatoid arthritis. Twenty eight patients with rheumatoid arthritis were studied. Each subject was subjected to a synovial biopsy in which a dry radioautographic technique for diffusable compounds was used. Patients were treated afterwards with 3 500mg iv pulses of methilprednisolone. A mean of 44.8 percent of synovial cells (range 30.1-62.8 percent) had binding sites for 3H dexamethasone. All patients had a significant clinical improvement after methilprednisolone. Multiple regression analysis did not show a correlation between clinical response and glucocorticoid receptor concentration. The lack of association between glucocorticoid receptor concentration and clinical response could be due to the large steroid dose used, that saturated all available receptors