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Background: Interferon (IFN) beta displays anti-inflammatory and immunosuppressive activity and has been considered for the treatment of rheumatoid arthritis (RA). Information about the effects of this molecule on joint cells is scarce, however.Objective: To investigate the effects of IFNbeta on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular chondrocytes and synovial fibroblasts.Methods: Chondrocytes and synovial fibroblasts were stimulated with IFNbeta alone or in combination with interleukin (IL) 1beta. IL1Ra concentrations in culture supernatants and cell lysates were determined by ELISA. Expression of mRNA encoding the secreted sIL1Ra or the intracellular icIL1Ra1 isoforms was quantified by real time reverse transcriptase-polymerase chain reaction.Results: In chondrocytes, IFNbeta alone had no effect, but dose dependently enhanced the secretion of IL1Ra induced by IL1beta. Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even after stimulation with IL1beta and IFNbeta. Consistently, IL1beta and IFNbeta induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra. In synovial fibroblasts, IFNbeta alone dose dependently increased IL1Ra secretion. In addition, IFNbeta enhanced the stimulatory effect of IL1beta on IL1Ra production. In synovial cell lysates, IFNbeta and IL1beta also increased IL1Ra levels. Consistently, IFNbeta and IL1beta induced the expression of both sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts.Conclusion: IFNbeta increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis. [ABSTRACT FROM AUTHOR]

Collagen-induced arthritis has been widely used as an animal model of rheumatoid arthritis. We have used this model with a view to determining potential therapeutic targets for the treatment of human disease. To do this we have attempted to modulate the progression of established arthritis over a 10-day time period following the first appearance of disease, by i.p. injection of one of three different MoAbs, These consist of a rat IgG2a specific for the CD5 antigen expressed on all T cells and a subpopulation of B cells, a mouse IgG2h recognizing the CD72 antigen, and a rat IgM specific for the B220 molecule, CD72 and B220 both being expressed on all B cells. None of the three MoAbs had depleting activity in vivo. The progression of arthritis was monitored both clinically, and histologically. The effects of treatment with anti-CD5 and anti-CD72 antibodies were compared with control antibodies of the same species class and subclass. In the case of anti- B220 antibodies, the effects of treatment were compared with administration of PBS, Of these MoAbs, only treatment with anti-CD5 resulted in disease amelioration with significant decrease in disease severity in 60% of the animals. These changes became apparent 6 days after initiation of treatment. There were no significant differences in serum levels of IgG antibodies to native bovine collagen type II between the groups of treated and control mice. Possible mechanisms underlying the modification of disease expression following treatment with anti-CD5 MoAb arc discussed. [ABSTRACT FROM AUTHOR]

In the blood of 10 patients with rheumatoid arthritis (RA), the number of TCR gamma;δ+T cells and CD5+B cells was 5.5%±4.38 and 34.3%±20.62 (mean±s.d.). respectively. In 12 patients with primary Sjögren's syndrome (SS) the mean ± s.d. of these T and B cell subpopulations was 47.5%± 38.5 and 38.75%±22.68. These values were significantly increased as compared with the circulating T and B cells from 22 healthy subjects in whom TCR γδ+T cells were 20.9 ±1.01 (P<0.001) for P<0.004 for SS) and CD5+B cells were 18.09%±4.47(P<0.001 for RA and SS). This increase was not influenced by disease activity. Furthermore, there was a marked correlation (P<0.001) between the levels of TCR γδ+T cells and CD5+B cells. This novel finding of coordinate elevated levels of lymphocytes with fetal phenotypes in RA and primary SS suggests an immunological imbalance that may have implications in these diseases. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin VH4 gene repertoire of eight IgM- and 10IgG-secreting synovial-derived hybridomas. The VH4 gene family is highly represented (38.5%) in this panel of hybridomas compared with the frequency of VH4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the VH4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of VH4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The VH gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of VH4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia. [ABSTRACT FROM AUTHOR]

Synovium was collected from 15 patients who were undergoing joint surgery. Two groups were defined by clinical diagnosis: patients with primary osteoarthritis (n = 4); and those with rheumatoid arthritis (n = 11). The synovium was studied using histological and morphometric techniques. In agreement with previous studies, no histological features specific for either diagnosis were found. A previously validated morphometric method was used to estimate the cellular density of randomly picked fields within defined areas of synovium. The mean nuclear density of cellularity of comparable areas of synovium was significantly different between these two disease states, but the mean nuclear density between individual representative samples within each clinical group was homogeneous. The morphometric analysis of lymphocyte subsets showed that within the upper synovial region and cellular aggregates in osteoarthritis, the distribution of T cells expressing the CD4 and CD8 antigen was the same. In rheumatoid arthritis CD8 cells predominated in the upper synovial region and CD4 cells in the cellular aggregates. Plasma cells were rarely found in osteoarthritic synovia, but were common in rheumatoid arthritis, with IgG-producing plasma cells predominating. Morphometric studies of representative synovial samples may help to improve histological diagnosis and our understanding of pathological mechanisms. [ABSTRACT FROM PUBLISHER]

The synovium from 11 patients with rheumatoid arthritis, who were undergoing joint surgery, was assessed using histological and morphometric techniques. Histological examination confirmed previous reports that the intensity of the cellular reaction varied throughout the synovium, and the morphometric method reflected this variability sensitively. The method was shown to be reproducible and allowed areas of similar cellular density to be defined. From these defined areas a total of 2.5 mm2 of synovium equivalent to 12 fields at x250 required analysis to reflect the variation in the cellular reaction. It would be feasible to collect this amount of material using an arthroscope. [ABSTRACT FROM PUBLISHER]

The article discusses the mechanisms involved in the cytotoxicity of microorganisms. The different cells include the cytolytic T lymphocytes which are affected by graft rejection and intracellular viral infection protection. Another are the natural killer cells that demonstrated an in vitro activity as interferon and its inducers contributed to the increase of its cytotoxicity while the antibody-dependent-cell-cytotoxicity cells acted directly on the effector.