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

Resistin-like molecule (RELM)-[beta] is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM-[beta] has a role in promoting airway inflammation and lung remodeling in the mouse lung. RELM-[beta] 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-[beta], we delivered recombinant routine RELM-[beta] intratracheally to halve mice. RELM-[beta] induced dose-dependent leukocyte accumulation (most prominently involving macrophages) and goblet cell hyperplasia. The most prominent effect induced by RELM-[beta] was increased perivascular and peribronchial collagen deposition. Mice genetically deficient in RELM-[beta] had reduced accumulation of collagen and goblet cell hyperplasia in an experimental model of allergic airway inflammation. In vitro experiments demonstrated that RELM-[beta] had fibroblast motogenic activity. These results identify RELM-[beta] as a Th2-associated cytokine with potent inflammatory and remodeling activity. lymphocytes; asthma; fibrosis