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[The significance of coagulation disorders and the inflammatory reaction in an infectious model of rheumatoid arthritis. II. Inhibition trials with antirheumatic drugs in the inflammatory reaction phase of erysipelas polyarthritis in rats].

The arthritic activity in the initial phase and during manifestation of experimental erysipelas in rats, an animal model for human rheumatoid arthritis, was studied by plethysmometrical methods. The development of body weight and specific pathologic alterations peculiar to the model such as keratitis, thrombosis of the aorta and gangrene of the tip of the tail served as additional parameters. In the volumetric analysis it could be shown that the first arthritic swelling on both hind legs develops symmetrically up to day 6 post infection in rats with about 200 g of body weight-and in contrast-on the 2nd p.i. in younger animals with about 120 g. The first maximal paw volume was measured on day 9 p. i., the greatest decrease in body weight-a reduction of 25%-on day 10 p. i. In addition the reaction of the animal model following the application of steroid and non-steroid symptomatically as well as cytostatically acting antirheumatic drugs was tested. Daily treatment with acetylsalicylic acid, indomethacine or hydrocortisone provoked more or less significant inhibition of arthritic swelling in the paw. Only at the onset of arthritis acetylsalicylic acid was more effective than the other antiphlogistic drugs. No measurable increase of paw volume during cyclophosphamide treatment could be evaluated. None of the antirheumatics used had a positive effect on body weight developement. In hydrocortisone and also in cyclophosphamide treated rats a greater decrease was obtained than in the infected controls. No thrombosis developed after cytostasis with cyclophosphamide. The advantages of this systemic connective tissue disease with regard to its comparability with human rheumatoid arthritis and due to the course of its arthritic manifestation are discussed, together with the disadvantages specific to the model and the experimental conditions.

Animals↗
PubMed1999

Human first trimester forebrain cells express genes for inflammatory and anti-inflammatory cytokines.

Using in situ hybridization and immunohistochemistry the induction of potential cytokines [interleukin 1beta (IL-1beta), IL-4, IL-6, IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta (TGF-beta)] in human embryonic forebrain cells at weeks 5, 7 and 10 of gestation was studied. The aims were to investigate the capacity of these cells to express cytokines, to determine the kinetics of induction and to display the type of cytokine expressing cells in the developing brain. Constitutive cytokine gene expression was recorded from week 5, augmented by about 50% at week 7 and by more than 100% at week 19 (except TGF-beta at week 10). Among other cytokines, IL-1beta exhibited the highest expression at week 10. TGF-beta showed maximum expression at week 7 and declined at week 10. Combined techniques revealed that glial cells are a major source of cytokines. The study show and present for the first time the kinetics of spontaneous cytokine expression in human embryonic forebrain cells. The increased mRNA expressions with age suggest an important role for cytokines in promotion of brain development. The capacity of inducing these cytokines may, however, be implicated in the immunopathogenesis of several brain diseases. The distinctive TGF-beta profile suggests a further role for TGF-beta on modulation of cytokine responses during development.

Cells, Cultured↗
PubMed2003

PAF-receptor in inflammatory versus non inflammatory human epidermis, cell cultures and embryonal cells.

OBJECTIVE: PAF-R (platelet activating factor-receptor) has been found on human keratinocytes to bind PAF, a proinflammatory phospholipid. We aimed to study PAF-R in a range of dermal cell lines and in samples of normal and psoriatic human skin to learn about its further role in humans. METHODS: PAF-R was labeled immunocytochemically, histochemically and additionally studied with western blotting in human keratinocytes, human fibroblasts, embryonal keratinocytes, tumor cell lines and samples of normal and psoriatic human skin. RESULTS: Keratinocytes from adult and embryonal epidermis of the 20th week of pregnancy showed a low level of labeling for PAF-R, but 3 +/- 0.05% of plantar keratinocytes from adults were positive as were 4.2 +/- 0.05% of embryonal plantar keratinocytes from the 21st week of pregnancy. In fibroblasts from adult and embryonal epidermis the protein was expressed at low levels. Western blotting revealed PAF-R positive bands at 67 k.Da in normal human skin and psoriasis, in psoriasis additionally at 45 k.Da. A 68 k.Da band was found in the colon cancer line HT 29 (control), and HaCaT cells, in embryonal keratinocytes additionally at 116 k.Da. CONCLUSIONS: PAF-R seems not to be important for embryonal or adult fibroblasts. In embryonal keratinocytes it is turned on after the 21st pregnancy week in a few cells seen as a band of 67 k.Da and at 116 k.Da, the latter is not found in adult keratinocytes. An additional 45 k.Da band of PAF-R was found in psoriasis that might stand for a truncated receptor. In the epithelial tumor cell line HaCaT and the HT29 colon cancer cell line PAF-R characterizes the anti-apoptotic effect of this receptor propagating tumor proliferation.

Adult↗