Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. II. Identification of (tissue) macrophages as the IL-1 producing cells and the effect of anti-inflammatory drugs.
We have used our newly described mouse tissue chamber model [1], to investigate the process of IL-1 production in more detail. The inflammatory reaction in the tissue surrounding the implanted chambers was investigated histologically and by using the polymerase chain reaction (PCR). The inflammatory response included influx of leucocytes into the granuloma surrounding the tissue chamber, expression of IL-1 beta on macrophages present in the inflamed tissue and an increase in the mRNA coding for IL-1 beta and IL-6 proteins in the granuloma. The effects of three anti-inflammatory or immunosuppressive drugs, prednisolone, indomethacin and cyclosporin A, on IL-1 beta and PGE2 production in zymosan and Bordetella-pertussis-vaccine (BPV)-challenged tissue chambers were also examined. Oral treatment with prednisolone and cyclosporin A of zymosan-challenged animals showed a dose-dependent reduction of IL-1 beta concentrations, but no effect of indomethacin. Both prednisolone and indomethacin dose-dependently reduced PGE2 concentrations to control levels, while cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). In drug-treated BPV-challenged animals, prednisolone and cyclosporin A also showed a dose-dependent reduction of IL-1 beta, while indomethacin was again ineffective. Prednisolone and indomethacin also dose-dependently reduced the PGE2 concentrations to control levels, whereas cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). This model will be useful for investigating the mechanisms controlling the production of IL-1 beta from the mRNA level to the secretion of mature biologically active protein [1], and in the search for new drugs which could selectively interfere with this process.
Dawson
J
J
Ciba-Geigy Ltd., Pharmaceuticals Division, Basel, Switzerland.
Rordorf-Adam
C
C
Geiger
T
T
Towbin
H
H
Kunz
S
S
Nguyen
H
H
Zingel
O
O
Chaplin
D
D
Vosbeck
K
K
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D015194:Diffusion Chambers, Culture; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006099:Granuloma / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010567:Pertussis Vaccine / Q000276:immunology; D016133:Polymerase Chain Reaction; D011239:Prednisolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015054:Zymosan / Q000276:immunology
D007375:Interleukin-1; D010567:Pertussis Vaccine; D012333:RNA, Messenger; D016572:Cyclosporine; D015054:Zymosan; D011239:Prednisolone; D015232:Dinoprostone; D007213:Indomethacin