Agents and Actions, vol. 28, 3/4 (1989) 0065-4299/89/040243-05 $1.50+ 0.20/0 91989 Birkh/iuserVerlag, Basel The release of interleukin-l-like activity by macrophages in two models of immunological inflammation in the rat C. Becherucci, D. Donati, M. Perretti and L. Parente 1 Sclavo ResearchCentre, Laboratoryof Pharmacology,Siena, Italy Abstract Interleukin-I (IL-I) is a putative mediator of inflammation released by activated macrophages in vitro. The IL-1 release by rat macrophages collected either from exudates in pertussis-induced air pouches or from the peritoneum during adjuvant arthritis has been investigated. In air pouch inflammation LPS- stimulated macrophages collected from sensitized animals release more IL-1 than cells from control rats at day 6 after challenge. This enhanced IL-1 release parallels the extent of mononuclear cell migration in the inflammatory lesion. In adjuvant arthritis LPS-stimulated macrophages collected from sensitized animals release more IL-I than cells from control rats at days 16 and 23 after adjuvant injection. The secondary inflammation in arthritic rats was statistically significant at days 16 to 28. These results indicate that during immunological inflammation macrophages either from the inflamed area or from a non-inflamed region release more IL-1 than control cells. This release parallels the extent of the inflammation and may be important in its pathogenesis. Introduction Interleukin-1 (IL-1) is a mediator released by acti- vated macrophages that is thought to play an im- portant role in modulating T lymphocyte activa- tion as well as in contributing to the pathogenesis of inflammatory diseases (see Ref. [1] for review). Most investigations have focused on IL-1 release by macrophages collected from control animals or healthy humans and activated in vitro by different stimuli [2-5]. On the other hand, there is little information on the IL-1 release by macrophages collected from inflammatory lesions or from blood or other natural sources during an ongoing inflam- matory process [6, 7]. In order to study macro- Author for correspondence: Dr. L. Parente, SclavoResearch Centre, Via Fiorentina, 53100 Siena, Italy. phage activation during immunological inflamma- tion, we have investigated the IL-1 release by mac- rophages collected from exudates in pertussis- induced air pouch inflammation and from the peri- toneum during adjuvant arthritis in the rat. Materials and methods Experimental inflammation The air pouch model was carried out according to Sedgwick et al. [8]. Male outbred Wistar rats (150 g body weight, Charles River, Calco, Italy) in light ether anesthesia were sensitized by subcuta- neous injection in both hind paws of B. pertussis vaccine (8.106 organisms/rat, Sclavo, Siena, Italy) in 0.2 ml Incomplete Freund's Adjuvant (IFA,