A-K Ulfgren

Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis.

OBJECTIVES--To develop and evaluate a new immunohistochemical method to study the localisation and phenotype of individual cytokine producing cells in synovial biopsy specimens in rheumatoid arthritis. METHODS--Cryopreserved sections of synovial tissue from nine patients with rheumatoid arthritis were incubated with carefully selected cytokine specific antibodies detecting 19 different cytokines, after fixation of the specimens with paraformaldehyde and using saponin to permeabilise the cell membranes. RESULTS--The immunohistochemical method yielded reproducible and distinct staining patterns, in which the cytokines accumulated mainly in the Golgi apparatus of producer cells, indicating that the method preferentially detected local synthesis rather than cytokine uptake. The cytokine production patterns varied considerably between biopsy specimens from different patients. CONCLUSION--The present modified immunohistochemical method may provide a simple and rapid way to determine the local production of a wide array of cytokines in the synovium. The data obtained with this method also indicated that more T cell derived cytokines than previously recognised were present in active synovitis, as located and sampled by arthroscopy.

Effects of anti-rheumatic treatments on expression of microsomal prostaglandin E synthase-1 in rheumatoid arthritis synovium

OBJECTIVE Microsomal prostaglandin E synthase 1 (mPGES-1) catalyzes the formation of PGE(2) from cyclooxygenase-derived PGH(2). Microsomal PGES-1 is induced by proinflammatory cytokines and is strongly linked to conditions that result in high PGE(2) biosynthesis. PGE(2) contributes to the pathogenesis of rheumatoid arthritis (RA), acting as a mediator of inflammation and promoting bone destruction. Induction of mPGES-1 in rheumatoid synoviocytes by proinflammatory cytokines has been demonstrated in vitro, indicating an important role in RA pathogenesis. Recent studies using mPGES-1-deficient mice demonstrated the importance of this gene in chronic inflammation. The aim of this study was to investigate the expression and localization of mPGES-1 in synovial biopsy specimens obtained from patients with RA. METHODS Synovial tissue samples from 24 patients with RA were obtained, and immunohistologic analysis was performed using polyclonal antibodies against mPGES-1. Double immunofluorescence staining was performed with antibodies to CD3, CD19, CD20, CD68, CD163, and prolyl 4-hydroxylase. RESULTS Intracellular mPGES-1 staining was observed in synovial membranes from all of the RA patients studied. Specifically, strong expression of mPGES-1 was detected in synovial lining cells. In sublining mononuclear and fibroblast-like cells, the extent of mPGES-1 staining was less than that in the synovial lining cells. In some patients, positive staining was observed in endothelial cells. With the double immunofluorescence technique, mPGES-1 production was detected in synovial macrophages and fibroblasts, while mPGES-1 expression was not observed in lymphocytes. CONCLUSION The demonstration of mPGES-1 expression in synovial tissues from patients with RA suggests a role for mPGES-1 in the RA disease process. Microsomal PGES-1 might be a potential new target for treatment strategies to control PGE(2) synthesis in patients with RA, without the systemic side effects associated with cyclooxygenase inhibitors.

Differential gene expression and protein expression levels of MMP and TIMP molecules in response to glucocorticoid treatment in arthritic patients

Differential gene expression and protein expression levels of MMP and TIMP molecules in response to glucocorticoid treatment in arthritic patients

Heterogeneity in cytokine profile after intra-articular steroid treatment

It is well known that intra-articular steroids are efficient and fast in reducing arthritis symptoms. However, treatment does not exclude long-term morbidity. Earlier studies have shown individual patterns in cytokine expression both inherently and in response to treatment. In this study we investigated the effect of ia steroids on the synovial tissue before and 10 days after treatment.

Increased apoptosis level in late stages of rheumatoid arthritis correlates with macrophage number

Rheumatoid arthritis (RA is a chronic inflammatory disease characterized by synovial hyperplasia and excessive mononuclear infiltration. Altered apoptosis was proposed as a possible mechanism for cell accumulation. In vitro experiments showed that monokines are able to inhibit synovial apoptosis in a dose dependent manner. In this study we aim to investigate synovial apoptosis with respect to disease duration, inflammatory cell type and monokines expression.