O. Huber-Bruning

Decrease in peripheral type 1 over type 2 T cell cytokine production in patients with rheumatoid arthritis correlates with an increase in severity of disease.

Objectives—To compare peripheral type 1 (T1) and type 2 (T2) T cell activities in rheumatoid arthritis (RA) patients with that found for osteoarthritic (OA) patients and healthy controls and to correlate peripheral T1/T2 cell activity in RA with parameters of the disease. METHODS Peripheral blood mononuclear cells were isolated from patients with RA (n=66), OA (n=19), and healthy controls (n=15). Primary T cell activity in these mononuclear cells was enhanced by means of anti-CD3/anti-CD28, which mimicks stimulation of T cells by activation of the T cell receptor and a major co-stimulatory signal. Interferon gamma (IFNγ) production and interleukin 4 (IL4) production in the three groups were quantified as measures of T1 and T2 cell activity, respectively, and compared. Serum tumour necrosis factor α (TNFα), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and joint destruction assessed radiographically of RA patients were determined as parameters of disease activity and correlated with T1/T2 cell activity. RESULTS Peripheral T cells from RA patients produced significantly less IFNγ and more IL4 than T cells from both age and sex matched OA patients and healthy controls. Moreover, in RA patients both a decrease in IFNγ and an increase in IL4 production correlated with an increase in serum TNFα, ESR, CRP, and joint destruction. Conclusions—These results suggest a role for differential T cell activity in RA. In view of the intra-articular T1 cell predominance the results might be explained by selective T1 cell migration into the joint or peripheral suppression of T1 cell activity.

Matrix depletion of young and old human articular cartilage by cultured autologous synovium fragments: a chondrocyte-independent effect

SummaryHuman articular cartilage of different ages was cultured for 8 days and proteoglycan (PG) release into the medium was measured. Retinol and synovial co-culture increased the PG release of cartilage of all ages. The effect of retinol was dose-dependent. Synovium increased also the PG release of dead cartilage, whereas retinol did not. The increased PG release by synovial co-culture is therefore mainly the result of synovial enzymes acting directly on the matrix rather than of a factor inducing chondrocyte-mediated breakdown.

In vitro influence of ketoprofen on the proteoglycan metabolism of human normal and osteoarthritis cartilage

We investigated the influences of ketoprofen on the proteoglycan (PG) turnover of human articular cartilage explants in three groups: normal young with a high basal PG synthesis, normal adult and osteoarthritis cartilage, both with a low basal PG synthesis. Ketoprofen had no influence on the mean PG synthesis rate of normal adult and OA cartilage after 4 days of culture nor on the cartilage PG content after 8 days of culture. There was no relation between the histological grade of OA and effects of ketoprofen. In normal young cartilage ketoprofen induced an increase of the PG synthesis rate when added to the culture in a concentration of 10−4M. No correlation existed between the effect of ketoprofen and the basal PG synthesis of normal cartilage.

Differential responses of old human cartilage explants to synovial- and mononuclear-cell factors

SummaryTo investigate mechanisms of cartilage destruction that may apply to rheumatoid arthritis, young and old human, and young porcine, articular cartilage was cultured for 8 days and the effects on proteoglycan (PG) metabolism of normal synovium supernatant (NSS), rheumatoid synovial fluid (RFL), and blood mononuclear cell supernatant (MCF) were studied. The effects were chondrocyte-mediated. An inverse correlation was found between baseline net PG synthesis and the effect of NSS on PG synthesis. Responses of young (porcine and human) cartilage were similar. In young cartilage the three agents induced PG depletion by suppression of net PG synthesis. In old cartilage NSS and RFL induced PG depletion, whereas MCF did not. In cartilage of low baseline net PG sysnthesis, NSS and MCF stimulated both PG release and PG synthesis; NSS stimulated predominantly PG release, and MCF predominantly PG synthesis. In conclusion, young and old human cartilage differ in the quality of their in vitro response to potentially catabolic factors. This may be due to the difference in baseline net PG synthesis. Synovial extracts differ from mononuclear-cell supernatants in their effects on old cartilage. It is suggested that this is caused by the presence, in different relative amounts, of factors that influence either PG synthesis or PG release.

Influence of rheumatoid synovial fluid and cells on proteoglycans in human cartilage explants. Modulation by piroxicam.

SummaryWe have studied the effects of cell-free rheumatoid synovial fluid (RASF) and the conditioned medium (CM) from these cells on the proteoglycans (PGs) of normal human cartilage and the influence which piroxicam might have on these processes. Both RASF and the CM from RASF cells enhanced the PG release from the cartilage explants. The effects of the above mentioned fluids on the cartilage PG content depended on the metabolic state of the cartilage i.e. correlated inversely with the PG synthesis. Whether this was due to the presence of anabolic and catabolic factors in these fluids is discussed. Piroxicam had no adverse effect on the PGs of human cartilage in vitro. Piroxicam prevented the cartilage PG depletion when it was induced by the CM from RASF cells.

Degradation of human cartilage by cytokines in vitro.

past history of ischaemic heart disease and was taking ibuprofen, digoxin, and frusemide. On examination a large fluctuant swelling of the shoulder extending posteriorly over the right deltoid and scapula was seen. The shoulder was cool but swollen and tender with limited movement. An x ray examination of the joint initially seemed to support the clinical diagnosis of Milwaukee shoulder with areas of abnormal lucency and sclerosis in the humeral head. Attempted aspiration of the joint was unsuccessful but a sample from the scapular swelling contained frank pus. On microscopy