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Interleukin-1 mimics the hyperalgesia induced by a factor obtained by macrophage lysis
J N Francischi1, B B Lorenzetti, S H Ferreira
1Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil.
Abstract:
1. 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.
Insights
A novel macrophage hyperalgesic factor (MHF) induces pain sensitivity in rats. This factor
Area of Science:
- Immunology
- Neuroscience
- Pain Research
Background:
- Macrophages are key immune cells involved in inflammation and pain signaling.
- The precise mediators released by macrophages that contribute to hyperalgesia are not fully understood.
Purpose of the Study:
- To identify and characterize a factor released by activated macrophages that induces hyperalgesia.
- To investigate the potential role of this factor in inflammatory pain models.
Main Methods:
- Lysis of stimulated rat peritoneal macrophages to isolate a low molecular weight factor (MHF).
- Injection of MHF into rat hind paws or peritoneal cavity to assess hyperalgesia.
- Testing the effect of indomethacin on MHF-induced hyperalgesia.
- Assessing MHF-like activity in carrageenin-induced peritonitis.
- Comparing MHF effects with human interleukin-1 (IL-1).
Main Results:
- Macrophage lysis released a low molecular weight factor (MHF) that induced bilateral hyperalgesia in rats.
- MHF activity was found in stimulated macrophages but not in neutrophils or resident macrophages.
- Indomethacin abolished MHF-induced hyperalgesia, suggesting prostaglandin involvement.
- MHF released prostaglandin-like material from guinea pig lung perfusate.
- Carrageenin-induced peritonitis showed hyperalgesia and MHF-like activity.
- Human IL-1 also induced hyperalgesia, abolished by indomethacin.
Conclusions:
- A macrophage-derived factor (MHF) contributes to inflammatory hyperalgesia.
- MHF likely acts via the release of cyclo-oxygenase products, such as prostaglandins.
- MHF may be related to or a fragment of interleukin-1 (IL-1).