This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0231OCv1 36/3/324    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsubara, S. Articles by Gelfand, E. W. Search for Related Content PubMed PubMed Citation Articles by Matsubara, S. Articles by Gelfand, E. W.

IL-2 and IL-18 Attenuation of Airway Hyperresponsiveness Requires STAT4, IFN-, and Natural Killer Cells

Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Erwin W. Gelfand, M.D., Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: gelfande{at}njc.org

IL-18 is known to induce IFN- production, which is enhanced when combined with IL-2. In the present study, we investigated whether the combination of exogenous IL-2 and IL-18 alters airway hyperresponsiveness (AHR) and airway inflammation. Sensitized mice exposed to ovalbumin (OVA) challenge developed AHR, inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and increases in levels of Th2 cytokines and goblet cell numbers. The combination of IL-2 and IL-18, but neither alone, prevented these changes while increasing levels of IL-12 and IFN-. The combination of IL-2 and IL-18 was ineffective in IFN-–deficient and signal transducer and activator of transcription (STAT)4-deficient mice. Flow cytometry analysis showed significant increases in numbers of IFN-–positive natural killer (NK) cells in the lung after treatment with the combination therapy, and transfer of lung NK cells isolated from sensitized and challenged mice treated with the combination significantly suppressed AHR and BAL eosinophilia. These data demonstrate that the combination of IL-2 and IL-18 prevents AHR and airway inflammation, likely through IL-12–mediated induction of IFN- production in NK cells.

Key Words: IL-2 • IL-18 • STAT4 • IFN- • airway hyperresponsiveness

CLINICAL RELEVANCE The data support the concept that manipulation of critical cytokines, in this case IL-2 and IL-18, can significantly impact allergic airway inflammation. Thus, the data support the use of these cytokines to interfere with asthma pathophysiology.

 

This article has been cited by other articles:

				M. S. Wilson, J. T. Pesce, T. R. Ramalingam, R. W. Thompson, A. Cheever, and T. A. Wynn Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells J. Immunol., November 15, 2008; 181(10): 6942 - 6954. [Abstract] [Full Text] [PDF]