This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0038OCv1 40/4/482    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 Churg, A. Articles by Wright, J. L. Search for Related Content PubMed PubMed Citation Articles by Churg, A. Articles by Wright, J. L.

The Role of Interleukin-1β in Murine Cigarette Smoke–Induced Emphysema and Small Airway Remodeling

¹ Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence and requests for reprints should be addressed to Andrew Churg, M.D., Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 Canada. E-mail: achurg{at}interchange.ubc.ca

Interleukin-1β (IL-1β), a proinflammatory cytokine, is elevated in cigarette smokers. To determine whether IL-1β plays a role in the pathogenesis of cigarette smoke–induced emphysema and small airway remodeling, IL-1 receptor knockout (IL1RKO), TNF- receptor knockout (TNFRKO), or C57Bl/6 (control) mice were exposed to cigarette smoke acutely or for up to 6 months. With a single acute exposure, smoke elevated IL-1β in C57Bl/6 mice. IL1RKO mice were protected against acute smoke–mediated increases in lavage inflammatory cells and matrix breakdown. In C57Bl/6 mice, acute smoke–mediated increases in inflammatory cells, serum IL-1β, and serum TNF- were blocked by z-VAD-fmk, a pan-caspase inhibitor, or z-WEHD-fmk, a caspase-1 (IL-1–converting enzyme, [ICE]) inhibitor. With 6 months of exposure, IL-1β was no longer increased, but IL-18 was elevated. After 6 months of exposure, IL1RKO mice were 65% protected against emphysema, whereas TNFRKO mice were 83% protected. Both strains were completely protected against small airway remodeling. Lavage desmosine, hydroxyproline, and hyaluronan, matrix breakdown markers, were elevated in C57 but not IL1RKO mice. We conclude that IL-1β plays a significant role in induction of murine emphysema and small airway remodeling, and is comparable to TNF- in its effects. The protective effects of caspase inhibitors appear to be related to inhibition of ICE and raise the question of whether models that ameliorate emphysema with caspase inhibitors are really blocking IL-1β (and IL-18) activation rather than blocking apoptosis.

Key Words: IL-1β • TNF- • cigarette smoke • emphysema • apoptosis

This article has been cited by other articles:

				K. B. Adler and S. Matalon Highlights of the October Issue Am. J. Respir. Cell Mol. Biol., October 1, 2009; 41(4): 377 - 378. [Full Text] [PDF]

				A. Churg and J. L. Wright Testing Drugs in Animal Models of Cigarette Smoke-induced Chronic Obstructive Pulmonary Disease Proceedings of the ATS, September 15, 2009; 6(6): 550 - 552. [Abstract] [Full Text] [PDF]