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-I beta modulates this action of IL-17. Methods: Intratracheal administration of human (h) IL-17 or rat (r) IL-1 beta or hIL-17 plus rIL-1 beta 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 mu g) increased the ELA and the MPO activity,as well as the neutrophil count in BAL fluid, whereas the proinflammatory cytokine rIL-1 beta (2.5 ng) did not. Pretreatment with rIL-1 beta 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. Conclusion: 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.