Recombinant human interleukin-8 is a potent activator of canine neutrophil aggregation, migration, and leukotriene B4 biosynthesis.
Interleukin-8 (IL-8), formerly known as NAP-1, is formed by a variety of cells upon stimulation with IL-1 or tumor necrosis factor (TNF). The biologic activity of the cytokine involves activation of almost every neutrophil function studied so far in different species. In the present study, we compared the effects of recombinant human IL-8 (rIL-8) and the lipid mediators, leukotriene B4 (LTB4) and platelet-activating factor (PAF), on neutrophil functions in dogs. All three chemotactic factors induced neutrophil aggregation and chemotaxis, with rIL-8 being far more potent than LTB4 and PAF. The migration induced by rIL-8 was significantly greater than that observed towards LTB4 and PAF. In the aggregation assay, rIL-8 was shown for the first time to be a potent stimulant. The aggregation response was more persistent than that obtained with LTB4 and PAF and the potency of rIL-8 was greater. An intradermal dose-response study showed that rIL-8 is an extremely potent inducer of selective neutrophil infiltration in canine skin. The infiltration was more pronounced than following injection of LTB4 or PAF. It was proposed that the superior effect of rIL-8 was caused by a synergistic effect between injected rIL-8 and LTB4, which was shown to be produced in biologically active amounts by canine neutrophils stimulated with rIL-8. From a therapeutic point of view, the simultaneous presence of rIL-8 and LTB4 in inflammatory skin diseases highlights the need to develop drugs that inhibit the production and/or effect of both mediators.
Thomsen
M K
MK
Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
Larsen
C G
CG
Thomsen
H K
HK
Kirstein
D
D
Skak-Nielsen
T
T
Ahnfelt-Rønne
I
I
Thestrup-Pedersen
K
K
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D002449:Cell Aggregation / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D007271:Injections, Intradermal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D007700:Kinetics; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects
D001095:Arachidonic Acids; D007375:Interleukin-1; D016209:Interleukin-8; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D007975:Leukotriene B4; D016718:Arachidonic Acid; D003513:Cycloheximide