Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo.
BACKGROUND
A recent study demonstrated that intratracheal administration of the T-lymphocyte cytokine IL-17 recruits neutrophils into airways in vivo by C-X-C chemokine release. It is not known whether IL-17 may also activate airway neutrophils.


OBJECTIVE
Our purpose was to evaluate whether IL-17 activates neutrophils in airways in vivo and, if so, whether the proinflammatory cytokine IL-1beta modulates this action of IL-17.


METHODS
Intratracheal administration of human (h) IL-17 or rat (r) IL-1beta or hIL-17 plus rIL-1beta in anesthetized, spontaneously breathing rats was followed by bronchoalveolar lavage (BAL) 6 hours later. The BAL fluid was characterized in terms of neutrophil count, of the activity for myeloperoxidase (MPO), and in some cases of the activity for elastase (ELA). Isolated rat neutrophils were stimulated with hIL-17 in vitro, followed by characterization of MPO activity in the cell medium.


RESULTS
hIL-17 (1 microg) increased the ELA and the MPO activity, as well as the neutrophil count in BAL fluid, whereas the proinflammatory cytokine rIL-1beta (2.5 ng) did not. Pretreatment with rIL-1beta enhanced IL-17induced ELA and MPO activity, without increasing the neutrophil count. The BAL ELA activity was inhibited by a specific inhibitor of neutrophil serine proteases. Stimulation with hIL-17 in vitro did not increase MPO activity in isolated neutrophils.


CONCLUSIONS
IL-17 can activate neutrophils in association with their recruitment into the airways in vivo and this effect is probably achieved through induced release of mediators from other airway cells.
Hoshino
H
H
Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden.
Laan
M
M
Sjöstrand
M
M
Lötvall
J
J
Skoogh
B E
BE
Linden
A
A
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004338:Drug Combinations; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020381:Interleukin-17 / Q000008:administration & dosage / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004338:Drug Combinations; D007375:Interleukin-1; D020381:Interleukin-17; D009195:Peroxidase; D019272:Leukocyte Elastase