Endogenous IL-11 signaling is essential in Th2- and IL-13-induced inflammation and mucus production.

Abstract

IL-11 and IL-11 receptor (R)alpha are induced by Th2 cytokines. However, the role(s) of endogenous IL-11 in antigen-induced Th2 inflammation has not been fully defined. We hypothesized that IL-11, signaling via IL-11Ralpha, plays an important role in aeroallergen-induced Th2 inflammation and mucus metaplasia. To test this hypothesis, we compared the responses induced by the aeroallergen ovalbumin (OVA) in wild-type (WT) and IL-11Ralpha-null mutant mice. We also generated and defined the effects of an antagonistic IL-11 mutein on pulmonary Th2 responses. Increased levels of IgE, eosinophilic tissue and bronchoalveolar lavage (BAL) inflammation, IL-13 production, and increased mucus production and secretion were noted in OVA-sensitized and -challenged WT mice. These responses were at least partially IL-11 dependent because each was decreased in mice with null mutations of IL-11Ralpha. Importantly, the administration of the IL-11 mutein to OVA-sensitized mice before aerosol antigen challenge also caused a significant decrease in OVA-induced inflammation, mucus responses, and IL-13 production. Intraperitoneal administration of the mutein to lung-specific IL-13-overexpressing transgenic mice also reduced BAL inflammation and airway mucus elaboration. These studies demonstrate that endogenous IL-11R signaling plays an important role in antigen-induced sensitization, eosinophilic inflammation, and airway mucus production. They also demonstrate that Th2 and IL-13 responses can be regulated by interventions that manipulate IL-11 signaling in the murine lung.

• Authors: Chun Geun Lee, Dominik Hartl, Hiroshi Matsuura, Felicity M Dunlop, Pierre D Scotney, Louis J Fabri, Andrew D Nash, Ning-Yuan Chen, Chu-Yan Tang, Qingsheng Chen, Robert J Homer, Manuel Baca, Jack A Elias
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 39 Issue 6 Pg. 739-46 (Dec 2008) ISSN: 1535-4989 [Electronic] United States
• PMID: 18617680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Allergens
• Interleukin-11
• Interleukin-13
• Mucin 5AC
• Receptors, Interleukin-11
• Tumor Necrosis Factor-alpha
• Ovalbumin

Topics

• Allergens (immunology)
• Animals
• Bronchoalveolar Lavage Fluid (cytology)
• Cell Count
• Gene Expression Regulation (drug effects)
• Immunization
• Inflammation (metabolism)
• Interleukin-11 (metabolism)
• Interleukin-13 (metabolism)
• Mice
• Mice, Inbred C57BL
• Mucin 5AC (genetics, metabolism)
• Mucus (metabolism)
• Ovalbumin (immunology)
• Phenotype
• Receptors, Interleukin-11 (metabolism)
• Signal Transduction (drug effects)
• Th2 Cells (drug effects, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)