Interleukin (IL)-6 release and fever induced by a pre-formed pyrogenic factor (PFPF) derived from LPS-stimulated macrophages

A novel pre-formed pyrogenic factor (PFPF), released by LPS-stimulated macrophages, has been identified, that induces an indomethacin-resistant fever. Its activity has to date not been found to match that of any described cytokine. In this study we observed that PFPF induced the release of large amounts of IL-6 from rat peritoneal macrophages. A combination of anti-cytokine antibodies and heat treatment excluded IL-1, tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS) as being responsible for this effect. PFPF also induced interleukin (IL)-1, IL-6 and TNF-α in a subcutaneous air pouch, as well as increasing plasma IL-6, and induced a fever of 0.58 ± 0.07° C (3 hours) that was not reduced by indomethacin (2 mg/kg, ip). Preparative isoelectric focusing (IEF) showed that the material responsible for inducing IL-6 release had a pI between 4.7 and 5.8 and corresponded to the IEF pool that induced fever when injected intracerebroventricularly.