Interleukin-8 as a mediator of sympathetic pain.
1. The hyperalgesic effects of interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta) and carrageenin were measured in a rat paw pressure test. 2. IL-8 evoked a dose-dependent hyperalgesia which was attenuated by a specific antiserum, the beta-adrenoceptor antagonists atenolol and propranolol, the dopamine receptor antagonist SCH 23390 and the adrenergic neurone-blocking agent guanethidine. The hyperalgesia was not attenuated by the cyclooxygenase inhibitor indomethacin or the IL-1 beta analogue Lys-D-Pro-Thr. 3. IL-1 beta-evoked hyperalgesia was attenuated by indomethacin and Lys-D-Pro-Thr but not by atenolol or SCH 23390. 4. Carrageenin-evoked hyperalgesia was attenuated by atenolol, indomethacin and anti-IL-8 serum. The effects of atenolol and anti-IL-8 serum were not additive. The effects of indomethacin and anti-IL-8 serum were additive: this combination abolished carrageenin-evoked hyperalgesia. 5. A new biological activity of IL-8 is described, namely the capacity to evoke hyperalgesia by a prostaglandin-independent mechanism. IL-8 is the first endogenous mediator to be identified as evoking hyperalgesia involving the sympathetic nervous system. Since IL-8 is released by activated macrophages and endothelial cells it may be a humoral link between tissue injury and sympathetic hyperalgesia.
Cunha
F Q
FQ
Department of Pharmacology, Faculty of Medicine, Sao Paulo, Brazil.
Lorenzetti
B B
BB
Poole
S
S
Ferreira
S H
SH
D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002351:Carrageenan; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D005528:Foot / Q000473:pathology; D006145:Guanethidine / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D001552:Benzazepines; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D001262:Atenolol; D002351:Carrageenan; D011433:Propranolol; D015232:Dinoprostone; D006145:Guanethidine