Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis. Proc Natl Acad Sci U S A. 2008 May 20;105(20):7240-5. Epub 2008 May 14.

IL-13 and IL-4 are central T helper 2 (Th2) cytokines in the immune system and potent activators of inflammatory responses and fibrosis during Th2 inflammation. Recent studies using Il13ra1(-/-) mice have demonstrated a critical role for IL-13 receptor (IL-13R) alpha1 in allergen-induced airway responses. However, these observations require further attention especially because IL-4 can induce similar lung pathology to IL-13, independent of IL-13, and is still present in the allergic lung. Thus, we hypothesized that IL-13Ralpha1 regulates IL-4-induced responses in the lung. To dissect the role of IL-13Ralpha1 and the type I and II IL-4Rs in experimental asthma, we examined lung pathology induced by allergen, IL-4, and IL-13 challenge in Il13ra1(-/-) mice. We report that IL-13Ralpha1 is essential for baseline IgE production, but Th2 and IgE responses to T cell-dependent antigens are IL-13Ralpha1-independent. Furthermore, we demonstrate that increased airway resistance, mucus, TGF-beta, and eotaxin(s) production, but not cellular infiltration, are critically dependent on IL-13Ralpha1. Surprisingly, our results identify a CCR3- and IL-13Ralpha1-independent pathway for lung eosinophilia. Global expression profiling of lungs from mice stimulated with allergen or IL-4 demonstrated that marker genes of alternatively activated macrophages are differentially regulated by the type I and type II IL-4R. Taken together, our data provide a comprehensive mechanistic analysis of the critical role by which IL-13Ralpha1 mediates allergic lung pathology and highlight unforeseen roles for the type II IL-4R.

Pathologic similarities and differences between asthma and chronic obstructive pulmonary disease.Curr Opin Pulm Med. 2008 Jan;14(1):31-8.

PURPOSE OF REVIEW: Classically, asthma and chronic obstructive pulmonary disease present distinct clinical, physiologic and pathologic features. However, not infrequently, patients may present with overlapping clinical symptoms and physiological abnormalities: patients with severe asthma may present with fixed airway obstruction and patients with chronic obstructive pulmonary disease may have hyperresponsiveness and eosinophilia. At pathological level, inflammatory and structural similarities also occur and may be related to the phenotypic overlaps. RECENT FINDINGS: In patients with asthma overlaps at inflammatory level exist with chronic obstructive pulmonary disease, such as increased neutrophilia in patients with severe asthma or an association of CD8+ T cells and lung-function decline. In chronic obstructive pulmonary disease, minimizing eosinophilia may be important to reduce exacerbations. Structural alterations occur in both diseases, but involving airway compartments differently. Airway epithelial changes, extracellular matrix deposition and mucus gland hypertrophy occur in both diseases. Asthmatics have thicker reticular basement membrane and more prominent smooth-muscle abnormalities, whereas emphysema is a distinct feature of chronic obstructive pulmonary disease. SUMMARY: Recognizing the differences and similarities at pathological level in both diseases may lead to a better understanding of the overlapping clinical and physiological phenotypes, thereby helping to better plan specific treatment and long-term management.