concanavalin-a and Arthritis--Reactive

Platelet factor 4 (PF-4) is a critical alpha chemokine in inflammation and injury responses, with multiple effects upon cellular activities. Discrete peptide sequences of the PF-4 molecule have been shown to retain biological activity. Our aim was to examine the influence of the PF-4 derived octapeptide (CT-112; TTSQVRPR) on type II collagen induced arthritis in mice, to determine if this peptide exhibited antiinflammatory properties.. DBA/1 mice were treated with CT-112 from either the time of immunization with type II collagen or from the initial onset of arthritis.. CT-112 both prevented the development of arthritis in mice treated prophylactically and reduced progression of disease in animals treated therapeutically, and was active when delivered by either subcutaneous injection or oral gavage. No marked immunosuppressive effects were observed during CT-112 treatment, with only moderate decrease in antibody levels and mitogen responses. A significant reduction of the circulating levels of IL-1 was a consistent finding in mice treated therapeutically with CT-112.. These data suggest PF-4 derived octapeptide exerts antiinflammatory effects of experimental arthritis in mice.

Topics: Administration, Oral; Amino Acid Sequence; Animals; Antibody Specificity; Arthritis, Reactive; Cell Division; Cells, Cultured; Collagen; Concanavalin A; Cytokines; Disease Models, Animal; Enzyme Inhibitors; Lipopolysaccharides; Mice; Mice, Inbred DBA; Mitogens; Peptide Fragments; Platelet Factor 4; Spleen; Tetrazolium Salts; Thiazoles; Thiazolidinediones

This study focuses on the consequences of T-lymphocyte activation in chronic polyarthritis in terms of expression of cell surface receptors interacting with extracellular matrix (ECM). The expression of the VLA group of integrins was studied on in vitro-stimulated peripheral-blood T cells, and on peripheral-blood and synovial-fluid mononuclear cells (MNC) of patients with polyarthritis. The VLA expression was measured by flow cytometry using monoclonal antibodies (MoAbs) against alpha-subunits of the VLA family. VLA-alpha 4 and VLA-alpha 5, but not VLA-alpha 1, were expressed on a major fraction of unstimulated peripheral-blood T cells both in the patients with polyarthritis and in healthy individuals. Two distinct populations, VLA-alpha 5-high and VLA-alpha 5-low, were found in resting peripheral-blood T lymphocytes. Two days after stimulation by phorbol 12-myristate 13-acetate (PMA) and concanavalin A, most T cells became VLA-alpha 5-high. In patients with chronic polyarthritis, the expression of VLA-alpha 1 and VLA-alpha 5 was always higher on synovial-fluid T cells than on peripheral-blood T cells. These results give further support to the hypothesis that upon activation the induction of the VLA adhesion-molecule expression may be a factor contributing to the accumulation of T cells in the inflamed synovium.

Topics: Adult; Aged; Arthritis, Reactive; Arthritis, Rheumatoid; Concanavalin A; HLA-DR Antigens; Humans; Lymphocyte Activation; Middle Aged; Receptors, Fibronectin; Synovial Fluid; T-Lymphocytes; Tetradecanoylphorbol Acetate

The T-cell mediated immunity in 21 patients with seronegative spondarthritis was tested with mitogens PHA, PWM, Con-A and MLC, and found to be reduced except when tested with Con-A. The patients were then treated with levamisole or placebo for 12 weeks in a double-blind trial. During treatment the T-cell responses normalized in both groups, and it is concluded that the enhanced response is independent of levamisole. Earlier we reported clinical improvement in levamisole treated patients and the data of the present study suggest that the effect of levamisole occurs locally in the inflamed tissues.

Topics: Adult; Arthritis, Reactive; Concanavalin A; Double-Blind Method; Female; Humans; Levamisole; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Spondylitis, Ankylosing; T-Lymphocytes

The influence of synovial fluid from four patients with Reiter's syndrome on lymphocyte responsiveness was studied. On synovial fluid was found which specifically depressed the responsiveness of lymphocytes from patients with Reiter's syndrome to the non-specific mitogen phytohaemagglutinin (PHA). The ratio of the responsiveness of lymphocytes cultured in the presence of foetal calf serum (FCS), compared to those incubated in the Reiter's synovial fluid, was used as a measure of the depression induced by the Reiter's synovial fluid. The mean ratio for eight normals stimulated with PHA was 0-70 (range 0-35-0-96), while for eight patients with Reiter's syndrome, it was 0-13 (range 0-07-0-19). Similar studies done with concanavalin A (con A) showed no difference between lymphocytes from normals (0-73) or patients with Reiter's syndrome (0-67). Chromatography of the Reiter's synovial fluid on a Sepharose 4-B column resulted in the separation of three major fractions, one of which exhibited the inhibitory activity. When this active fraction was absorbed with Reiter's lymphocytes, a loss of the inhibitory activity of the fraction was seen. A similar absorption with normal lymphocytes had no effect. These studies demonstrate that a factor present in the synovial fluid of a patient with Reiter's syndrome reacted specifically with lymphocytes from patients with Reiter's disease and not with lymphocytes from normals. The interaction of this factor with lymphocytes from patients with Reiter's syndrome inhibited the responsiveness of these lymphocytes to PHA but not to con A.

Topics: Adult; Arthritis, Reactive; Arthritis, Rheumatoid; Chromatography; Concanavalin A; Humans; Lectins; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Synovial Fluid