[Experimental studies on the immunopathogenesis of chronic hepatitis].
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Biomedical subjects
Publications and source records attributed to H Warnatz.
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Peripheral blood monocytes (PBMo) and synovial fluid macrophages (SFMO) of patients with rheumatoid arthritis (RA), HLA B27-positive reactive oligoarthritis and controls were investigated for their capacity to generate superoxide anions (O2-) upon stimulation with phorbolmyristoacetate (PMA) in a cytochrome c (cyt c) microassay. PBMo of RA patients, patients with reactive arthritis and controls did not reveal any significant differences and also treatment of RA patients with gold salts or immunosuppressive therapy had no effect on the oxidative burst in PBMo. In contrast, in SFMO of RA patients treated only with nonsteroidal anti-inflammatory drugs (NSAID) we found significantly enhanced O2- release, compared with PBMo of the same group. Treatment with gold salts had no effect on this enhanced oxidative response, whereas immunosuppressive therapy with azathioprin or corticosteroids significantly reduced the O2- release of SFMO. In patients suffering from reactive arthritis we did not find significant differences between SFMO and PBMo. The O2- release of SFMO of this group was significantly reduced, when compared to that of SFMO of RA patients, treated with NSAID. These results indicated that SFMO but not PBMo in RA in cyt c microassay produce increased levels of activated oxygen species. In comparison to PBMo, SFMO of patients suffering from reactive arthritis do not show such an increased oxidative burst. These findings suggest that in RA, activated oxygen species have a local destructive effect in inflamed joints. This seems to be caused by activation of catalytic enzymes and complement components, as well as induction of release of interleukins or prostaglandins, contributing to the augmentation of the chronic inflammatory process.
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Lymphocytotoxicity to autologous or allogeneic synovial cells and Chang cells was studied in 27 patients with rheumatoid arthritis (RA), in 5 patients with osteoarthrosis of the hip or knee and in 17 healthy controls. Ficoll gradient-separated lymphocytes from the peripheral blood, T cells and non-T cells were used as effector cells. T lymphocytes were isolated as E-rosette forming cells 10 percent of which carried Fc- receptors. The differential counts for T and B cells in the peripheral blood of the RA and osteoarthrosis patients were approximately the same as in the blood of the healthy controls. The counts of Fc-receptor-bearing cells in the RA patients were, however, significantly higher. Cytotoxic reactivity of lymphocytes from RA patients, osteoarthrosis patients or healthy controls to synovial cells of autologous or allogeneic origin could not be demonstrated in our study, in which 125I-iododeoxyuridine labelled target cells were used in the microcytotoxicity test of Cohen et al. However, lymphocytes of the peripheral blood showed an increased cytotoxicity to Chang cells, an effect for which Fc-receptor bearing cells were responsible. Serum did not affect the cytotoxicity of lymphocytes. The results are interpreted as demonstrating an enhanced natural killer (NK) cell activity in RA patients; they do not indicate a specific cell mediated immune reaction to synovial cells.
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Seronegative rheumatoid arthritis (RA) patients have increased proportions of OKT-4+ (helper) T cells and diminished proportions of OKT-8+ (suppressor/cytotoxic) T cells in the peripheral blood. This phenomenon corresponds to diminished inhibition of B cell activation by peripheral blood lymphocytes (PBL). Seropositive RA patients show a broad range of OKT-8+ T cell proportions (9%-45%) in the peripheral blood, resulting in a mean level comparable to that in controls. Inhibition of T cell activation by suppressor cells in peripheral blood is greater in this group than in controls. HLA-B27-positive arthritis patients show no significant differences from controls with respect to markers and functional suppressor cell assays. In the synovial fluid of all patients both OKT-8+ T cell proportions and functional suppressor cell activity are greatly increased.