The role of macrophages in inflammation.
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Biomedical subjects
Publications and source records attributed to M Seitz.
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The present study was designed to characterize leukocytes of patients with rheumatoid arthritis (RA) with regard to proliferation of peripheral blood lymphocytes (PBL) and prostanoid release from circulating monocytes (M phi. Compared to cells of healthy individuals, PBL from RA patients exhibited a reduced mitogenic response to concanavalin A (Con A) which was associated with an increased capacity of circulating M phi to synthesize PGE and thromboxane B2 (TXB2). Addition of synovial fluid exudates of RA patients (RA-SFE) to peripheral blood leucocyte cultures produced three effects: A spontaneous proliferation of normal and RA-PBL, a reduction of the Con A response of normal and RA-PBL, a reduction of the Con A response of normal and RA-PBL, and an enhanced release of PGE and TXB2 from RA-M phi only. To elucidate the cellular origin of these activities, normal and RA-PBL were incubated with supernatants (SNT) os synovial cell cultures from RA patients and patients with non-RA joint diseases. SNT from Con A-stimulated synovial lymphocytes of both RA and control patients induced a spontaneous proliferation of normal and RA-PBL. In contrast, SNT from non-lymphoid adherent synovial cells of RA and control patients reduced the Con A response of normal and RA-PBL but a striking difference was noted in that an enhanced PGE and TXB2 release occurred only from M phi of RA patients.
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PGE and PGF release from peritoneal exudate cells was studied in mice after injection with two beta (1-3) glucans, the antitumor active lentinan and the inactive pachyman, 4 days after injection of both polysaccharides, the spontaneous and phagocytosis-induced PGE and PGF release was markedly suppressed. However, only the immunopotentiator lentinan induced peritoneal exudate cells which exhibited a longer lasting diminished PG release. The data suggest that the T cell adjuvant lentinan may potentiate cellular immune responses by reducing synthesis of immune suppressive prostaglandins from peritoneal exudate cells.
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In a clinical phase II trial the efficacy and side effects of recombinant human interferon gamma in 13 patients with rheumatoid arthritis (RA) are reported. 2 patients (15.3%) showed a marked improvement of rest- and motion pains and of their general motility after a 6 and 8 month treatment. Only a temporary improvement within 2-3 months was observed in 4 patients (30.7%). In 2 cases a reduction of the erythrocyte sedimentation rate and in 4 cases a reduction of the alpha-1 acid glycoprotein and of the number of thrombocytes was documented parallel to the clinical improvement. 3 patients developed new antinuclear antibodies (ANA) or showed an increased titer of ANA. Fever was the most common side effect followed by lymphopenia and increased liver values. All side effects were reversible after dosage reduction. Our results confirm the relatively good short term efficacy of human recombinant interferon gamma in RA. In contrast, the clinical long term benefit remains doubtful.
We tested the efficacy of the immunomodulator Bestatin, which has been successfully applied in Japan, in a preliminary open study in ten patients with classical or definite rheumatoid arthritis. Patients whose arthritis was characterized by a low humoral activity showed a partial remission of the disease after six months' application of increasing doses of 10-60 mg in 48 hours. We found a significant increase in superoxide release from peripheral monocytes. Humoral parameters of inflammation such as erythrocyte sedimentation rate, C3a complement fraction, prostaglandin E2, and thromboxane B2 decreased. Concerning the subpopulations of lymphocytes we found a slight increase of activated T-lymphocytes and a decrease of O-cells and B-cells. The T-helper/T-suppressor ratio remained unchanged. The rheumatoid factor and the antinuclear antibodies showed no alteration under the treatment. Two weeks after withdrawal of Bestatin the improvement of the clinical and humoral parameter of the inflammation in rheumatoid arthritis vanished. No serious side effects were seen. Our results contribute to a long-term controlled study of the immunomodulator Bestatin as basic drug in the treatment of rheumatoid arthritis.