Lysis of rat thioglycolate-stimulated peritoneal macrophages releases a low molecular weight factor (0.5 less than MW less than 10 kD) into the supernatant. Bilateral hyperalgesia was observed when this factor, denoted macrophage hyperalgesic factor (MHF), was injected into one hind paw or into the peritoneal cavity of the rat. 2. Similar activity was detected in stimulated peritoneal and tumoral mouse macrophages (J774G8) but not in lysates of rat exudate neutrophils or in peritoneal resident (non-stimulated) macrophages. 3. The hyperalgesia induced by MHF was abolished by local intraplantar injection of indomethacin, thus suggesting a peripheral release of cyclo-oxygenase products. This suggestion was supported by the ability of MHF to release prostaglandin-like material when added to a guinea pig lung perfusate. 4. Peritonitis induced by the administration of carrageenin caused concomitant bilateral rat paw hyperalgesia and an MHF-like activity was demonstrable in peritoneal exudate 30 min after the carrageenin insult. 5. Purified human interleukin-1 (IL-1) given locally or systemically also produced bilateral hind paw hyperalgesia which was abolished by local administration of indomethacin. The possibility that MHF may be a fragment of IL-1 is discussed.
