INTERLEUKIN-1 (IL-1) PRODUCTION IN A MOUSE-TISSUE CHAMBER MODEL OF INFLAMMATION .2. IDENTIFICATION OF (TISSUE) MACROPHAGES AS THE IL-1 PRODUCING CELLS AND THE EFFECT OF ANTIINFLAMMATORY DRUGS

We have used our newly described mouse tissue chamber model 1!, to in vestigate the process of IL-1 production in more detail. The inflammat ory reaction in the tissue surrounding the implanted chambers was inve stigated histologically and by using the polymerase chain reaction (PC R). The inflammatory response included influx of leucocytes into the g ranuloma surrounding the tissue chamber, expression of IL1beta on macr ophages present in the inflamed tissue and an increase in the mRNA cod ing for IL-1beta and IL-6 proteins in the granuloma. The effects of th ree anti-inflammatory or immunosuppressive drugs, prednisolone, indome thacin and cyclosporin A, on IL-1beta and PGE2 production in zymosan a nd Bordetella-pertussis-vaccine (BPV)-challenged tissue chambers were also examined. Oral treatment with prednisolone and cyclosporin A of z ymosan-challenged animals showed a dose-dependent reduction of 1beta c oncentrations, but no effect of indomethacin. Both prednisolone and in domethacin dose-dependently reduced PGE2 concentrations to control lev els, while cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). In drug-treated BPV-challenged animals, prednis olone and cyclosporin A also showed a dose-dependent reduction of IL-1 beta, while indomethacin was again ineffective. Prednisolone and indom ethacin also dose-dependently reduced the PGE2 concentrations to contr ol levels, whereas cyclosporin A was effective only at the highest dos e tested (100 mg/kg/day p.o.). This model will be useful for investiga ting the mechanisms controlling the production of IL-1beta from the mR NA level to the secretion of mature biologically active protein 1!, a nd in the search for new drugs which could selectively interfere with this process.