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EDITORIAL FOCUS

Resistin-like molecule- is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung

¹Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio; and ²Regeneron Pharmaceuticals, Incorporated, Tarrytown, New York

Submitted 16 April 2007 ; accepted in final form 27 May 2007

Resistin-like molecule (RELM)- is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM- has a role in promoting airway inflammation and lung remodeling in the mouse lung. RELM- is strongly induced by diverse allergens and T helper type 2 (Th2) cytokines by an IL-13- and STAT6-dependent mechanism. To understand the in vivo role of RELM-, we delivered recombinant murine RELM- intratracheally to naïve mice. RELM- induced dose-dependent leukocyte accumulation (most prominently involving macrophages) and goblet cell hyperplasia. The most prominent effect induced by RELM- was increased perivascular and peribronchial collagen deposition. Mice genetically deficient in RELM- had reduced accumulation of collagen and goblet cell hyperplasia in an experimental model of allergic airway inflammation. In vitro experiments demonstrated that RELM- had fibroblast motogenic activity. These results identify RELM- as a Th2-associated cytokine with potent inflammatory and remodeling activity.

lymphocytes; asthma; fibrosis

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