Neutrophil recruitment by interleukin-17 into rat airways in vivo. Role of tachykinins.
We determined whether neutrophil recruitment induced by the T-lymphocyte cytokine, interleukin-17 (IL-17) is modulated by tachykinins in airways in vivo. Cell recruitment into airways was induced by either human (h) IL-17 (1 microgram) or rat (r) IL-1beta (2. 5 ng), instilled intratracheally in rats (n = 5 to 7). Six hours after instillation, hIL-17 (3.1 +/- 1.2 x 10(6) cells/ml) and rIL-1beta (4.1 +/- 0.5 x 10(6) cells/ml), respectively, induced a significant and selective increase in neutrophil count in bronchoalveolar lavage fluid (BAL) when compared with vehicle (0.6 +/- 0.2 x 10(6) cells/ml). For hIL-17, this effect was dose-dependent. Inhalation of peptidase inhibitors (phosphoramidon plus captopril) potentiated the effect of both hIL-17 and rIL-1beta. Inhalation of a neutral endopeptidase inhibitor (phosphoramidon) alone also increased the neutrophil count for hIL-17, whereas an angiotensin-converting enzyme inhibitor (captopril) alone did not. A selective neurokinin (NK)-1 receptor antagonist (SR 140333) reduced the neutrophil count, both with and without phosphoramidon pretreatment. In conclusion, IL-17 selectively recruits neutrophils into rat airways in vivo and this effect is modulated by endogenous tachykinins acting via NK-1 receptors.
Hoshino
H
H
Department of Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden.
Lötvall
J
J
Skoogh
B E
BE
Lindén
A
A
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology; D020381:Interleukin-17 / Q000008:administration & dosage / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea
D004338:Drug Combinations; D007375:Interleukin-1; D020381:Interleukin-17; D064729:Neurokinin-1 Receptor Antagonists; D011480:Protease Inhibitors