Pathology Of Allergic Asthma Research Articles

Eosinophil expression of triggering receptor expressed on myeloid cells 1 (TREM-1) restricts type 2 lung inflammation.

Asthma affects 25 million Americans, and recent advances in treatment are effective for only a portion of severe asthma patients. TREM-1, an innate receptor that canonically amplifies inflammatory signaling in neutrophils and monocytes, plays a central role in regulating lung inflammation. It is unknown how TREM-1 contributes to allergic asthma pathology. Utilizing a murine model of asthma, flow cytometry revealed TREM-1+ eosinophils in the lung tissue and airway during allergic airway inflammation. TREM-1 expression was restricted to recruited, inflammatory eosinophils. Expression was induced on bone marrow-derived eosinophils by incubation with interleukin 33, lipopolysaccharide, or granulocyte-macrophage colony-stimulating factor. Compared to TREM-1- airway eosinophils, TREM-1+ eosinophils were enriched for proinflammatory gene sets, including migration, respiratory burst, and cytokine production. Unexpectedly, eosinophil-specific ablation of TREM-1 exacerbated airway interleukin (IL) 5 production, airway MUC5AC production, and lung tissue eosinophil accumulation. Further investigation of transcriptional data revealed apoptosis and superoxide generation-related gene sets were enriched in TREM-1+ eosinophils. Consistent with these findings, annexin V and caspase-3/7 staining demonstrated higher rates of apoptosis among TREM-1+ eosinophils compared to TREM-1- eosinophils in the inflammatory airway. In vitro, Trem1/3-/- bone marrow-derived eosinophils consumed less oxygen than wild-type in response to phorbol myristate acetate, suggesting that TREM-1 promotes superoxide generation in eosinophils. These data reveal protein-level expression of TREM-1 by eosinophils, define a population of TREM-1+ inflammatory eosinophils, and demonstrate that eosinophil TREM-1 restricts key features of type 2 lung inflammation.

Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction.

Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy causes alveolar dysfunction contributing to the pathology of allergic asthma remains unaddressed. To explore whether airway allergy causes alveolar dysfunction that might contribute to the pathology of allergic asthma, alveolar structural and functional alterations were analyzed during house dust mite (HDM)-induced airway allergy in mice, by flow cytometry, light and electron microscopy, monocyte transfer experiments, assessment of intra-alveolarly-located cells, analysis of alveolar macrophage regeneration in Cx3cr1 cre:R26-yfp chimeras, analysis of surfactant-associated proteins, and study of lung surfactant biophysical properties by captive bubble surfactometry. Our results demonstrate that HDM-induced airway allergic reactions caused severe alveolar dysfunction, leading to alveolar macrophage death, pneumocyte hypertrophy and surfactant dysfunction. SP-B/C proteins were reduced in allergic lung surfactant, that displayed a reduced efficiency to form surface-active films, increasing the risk of atelectasis. Original alveolar macrophages were replaced by monocyte-derived alveolar macrophages, that persisted at least two months after the resolution of allergy. Monocyte to alveolar macrophage transition occurred through an intermediate stage of pre-alveolar macrophage and was paralleled with translocation into the alveolar space, Siglec-F upregulation, and downregulation of CX3CR1. These data support that the severe respiratory disorders caused by asthmatic reactions not only result from bronchiolar inflammation, but additionally from alveolar dysfunction compromising an efficient gas exchange.

Reduced CCR6+IL-17A+Treg Cells in Blood and CCR6-Dependent Accumulation of IL-17A+Treg Cells in Lungs of Patients With Allergic Asthma.

Human regulatory T (Treg) cells play a central role in controlling allergic inflammation in the airways. A reduced number of peripheral Treg cells and decreased suppressive function have been previously reported in the pathogenesis of allergic asthma. However, the characteristic role of specific Treg cell subsets and their mechanisms in the pathogenesis of allergic asthma remain unclear. In this study, we examined the proportion of different Treg cell subsets in both healthy subjects and patients with allergic asthma using flow cytometry and single-cell RNA sequencing. The migration function of the cells was compared using cell sorting and Transwell experiments. Furthermore, two allergen-challenged mouse models and a cell transfer experiment were used to examine the role of these Treg subsets. We found that the proportion of CD25+Foxp3+CD127- Treg cells in the peripheral blood of patients with allergic asthma was lower than in those of healthy subjects. Furthermore, the circulating Treg cells expressed lower levels of CCR6 and IL-17 compared with healthy subjects. The chemokine from the airway mucosa, CCL20, was abundantly expressed, and Transwell experiments further proved that this chemokine promoted CCR6+ Treg cell migration in vitro. A mouse model induced by house dust mite (HDM) revealed that the number of CCR6+ Treg cells in the lung tissue increased remarkably. The incidence of allergic asthma may be related to an increase in Treg cells secreting IL-17 in the lung tissue. Recruited CCR6+ Treg cells are likely to differentiate into Th17-like cells under the Th17 environment present in the lungs. IL-17 derived from Th17-like cells could be associated with the pathology of allergic asthma by promoting Th17 responses, thereby favoring HDM-induced asthma exacerbations.

Study effect of Baicalein encapsulated/loaded Chitosan-nanoparticle on allergic Asthma pathology in mouse model.

Asthma as chronic airway disease has high prevalence in children and imbalance of Th1/Th2 is a critical mechanism in pathogenesis of the asthma. Baicalein as a cell protective and anti-inflammatory flavonoid may have anti-asthma effect. Therefore, for better using lung, baicalein was used in chitosan-nanoparticle as anti-asthma treatment. Baicalein was loaded and encapsulated in chitosan nanoparticle. The morphology, physical characters (particle size, zeta potential and FT-IR) were analyzed. Drug encapsulation and loading capacity, accumulative release-time were studied. After asthma model producing, the mice were treated with L-B-NP and E-B-NP. At least, MCh challenge test, Cytokines measurement and Lung Histopathology were done. Nanoparticles had average size 285±25nm with negative charge -2.5mV. The L-B-NP decreased penh value and E-B-NP decreased inflammation. Both nanoparticles increased IL-12 and decreased IL-5. Also, L-B-NP decreased mucus secretion in bronchi. L-B-NP and E-B-NP control immune-allergo-inflammatory response of asthma. L-B-NP controlled AHR and E-B-NP controlled inflammation that can be used as controlling anti-asthma drug.

Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma.

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then distributing cytokine cues to elicit type 2 immune effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery.

TLR9\u2013IL-2 axis exacerbates allergic asthma by preventing IL-17A hyperproduction

Allergic asthma is one of most famous allergic diseases, which develops lung and airway inflammation. Recent studies have revealed the relationship between the pathology of allergic asthma and the increase of host-derived DNA in inflamed lung, but the role of the DNA-recognizing innate immune receptor for the inflammation is unknown well. Here we investigated the role of Toll-Like Receptor 9 in the pathogenesis of allergic asthma without synthesized CpG-ODNs. To examine that, we analyzed the pathology and immunology of house-dust-mite (HDM)-induced allergic asthma in Tlr9–/– mice and TLR9-inhibitory-antibody-treated mice. In Tlr9–/– mice, airway hyperresponsiveness (AHR) and the number of eosinophils decreased, and production of the Th2 cytokines IL-13, IL-5, and IL-4 was suppressed, compared with in wild-type mice. Interestingly, unlike Th2 cytokine production, IL-17A production was increased in Tlr9–/– mice. Furthermore, production of IL-2, which decreases IL-17A production, was reduced in Tlr9–/– mice. Blockade of TLR9 by treatment with TLR9-inhibitory-antibody, NaR9, effectively suppressed the development of allergic asthma pathology. IL-17A production in NaR9-treated mice was enhanced, which is comparable to Tlr9-/- mice. These results suggest that the TLR9–IL-2 axis plays an important role in Th2 inflammation by modulating IL-17A production in HDM-induced allergic asthma and that targeting of TLR9 might be a novel therapeutic method for allergic asthma.

IL-10 production by ILC2s requires Blimp-1 and cMaf, modulates cellular metabolism, and ameliorates airway hyperreactivity

Group 2 innate lymphoid cells (ILC2s) are the dominant innate lymphoid cell population in the lungs at steady state, and their release of type 2 cytokines is a central driver in responding eosinophil infiltration and increased airway hyperreactivity. Our laboratory has identified a unique subset of ILC2s in the lungs that actively produce IL-10 (ILC210s). Our aim was to characterize the effector functions of ILC210s in the development and pathology of allergic asthma. IL-4-stimulated ILC210s were isolated to evaluate cytokine secretion, transcription factor signaling, metabolic dependence, and effector functions invitro. ILC210s were also adoptively transferred into Rag2-/-γc-/- mice, which were then challenged with IL-33 and assessed for airway hyperreactivity and lung inflammation. We have determined that the transcription factors cMaf and Blimp-1 regulate IL-10 expression in ILC210s. Strikingly, our results demonstrate that ILC210s can utilize both autocrine and paracrine signaling to suppress proinflammatory ILC2 effector functions invitro. Further, this subset dampens airway hyperreactivity and significantly reduces lung inflammation invivo. Interestingly, ILC210s demonstrated a metabolic dependency on the glycolytic pathway for IL-10 production, shifting from the fatty acid oxidation pathway conventionally utilized for proinflammatory effector functions. These findings provide an important and previously unrecognized role of ILC210s in diseases associated with ILC2s such as allergic lung inflammation and asthma. They also provide new insights into the metabolism dependency of proinflammatory and anti-inflammatory ILC2 phenotypes.

Nanoparticle-based thymulin gene therapy therapeutically reverses key pathology of experimental allergic asthma.

Despite long-standing efforts to enhance care for chronic asthma, symptomatic treatments remain the only option to manage this highly prevalent and debilitating disease. We demonstrate that key pathology of allergic asthma can be almost completely resolved in a therapeutic manner by inhaled gene therapy. After the disease was fully and stably established, we treated mice intratracheally with a single dose of thymulin-expressing plasmids delivered via nanoparticles engineered to have a unique ability to penetrate the airway mucus barrier. Twenty days after the treatment, we found that all key pathologic features found in the asthmatic lung, including chronic inflammation, pulmonary fibrosis, and mechanical dysregulation, were normalized. We conducted tissue- and cell-based analyses to confirm that the therapeutic intervention was mediated comprehensively by anti-inflammatory and antifibrotic effects of the therapy. We believe that our findings open a new avenue for clinical development of therapeutically effective gene therapy for chronic asthma.

The synergistic or adjuvant effect of DINP combined with OVA as a possible mechanism to promote an immune response

Diisononyl phthalate (DINP) is commonly used as a plasticizer in industrial and consumer product applications. Several studies have suggested a possible link between exposure to DINP and the development of allergic asthma, and the synergistic effect of DINP combined with Ovalbumin (OVA) is a possible way to promote an immune response. These findings are still speculative, since there is insufficient evidence to assess the ability of DINP to influence “allergic asthma pathology”. This study was designed to determine any effects of OVA/DINP exposure on airway reactivity, particularly when combined with allergen exposure. Experiments to determine these effects were conducted after 15 days of combined exposure and a subsequent challenge with aerosolized ovalbumin for one week. Airway hyper-responsiveness (lung function), lung tissue pathology, cytokines and oxidative stress biomarkers were investigated. We showed that oral exposure to OVA/DINP could induce airway hyper-responsiveness (AHR), and aggravate airway wall remodeling, and that this deterioration was concomitant with increased immunoglobulin-E and Th2 cytokines secretion. The data also demonstrated that DINP could promote oxidative damage in the lung. In summary, this study showed that DINP has an adjuvant effect on allergic asthma affecting lung function, lung histopathology, immune molecules and causes oxidative damage.

ATP/P2X7r axis mediates the pathological process of allergic asthma by inducing M2 polarization of alveolar macrophages

Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1β and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization.

IL-25 Orchestrates Activation of Th Cells via Conventional Dendritic Cells in Tissue to Exacerbate Chronic House Dust Mite-Induced Asthma Pathology.

House dust mite (HDM) extract is a common trigger of asthma in humans. Chronic exposure to HDM also induces asthma-like pathology in mice. Allergic responses to HDM and other allergens are linked to release of IL-25, IL-33, and TSLP by epithelial cells; these cytokines, especially IL-33, target innate lymphoid cells type 2 to produce type 2 cytokines. To what extent and by what mechanisms IL-25 contributes to chronic HDM-induced pathology is not well understood. In humans, elevated levels of IL-25 appear to be associated with cases of uncontrolled asthma and exacerbated attacks. In this article, we demonstrate that blockade of IL-25 signaling in either lung conventional dendritic cells or in T cells resulted in similar decreases in production of IL-13 and IL-9 by T cells, reduced mast cell accumulation and tissue remodeling, and improved lung function but had only modest effects on eosinophilia. Stimulation of conventional dendritic cells by IL-25 promoted proximal accumulation of Th cells, and stimulation of Th cells by IL-25 locally promoted IL-13 and IL-9 production. IL-25 made notable contributions to chronic HDM-induced allergic asthma pathology by facilitating clustering and cross-stimulation of different cell types in tissue. Therapeutic targeting of IL-25 in combination with other treatments may be beneficial.

Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation.

BackgroundMigration of leukocytes into airways is the hallmark of allergic asthma. The aim of this study was to target the pathological process using pantethine, a pleiotropic natural compound which has been recently shown to down-regulate chemokine-driven T cell migration.Material/MethodsMice were sensitized to the Leishmania LACK antigen, then treated or not treated with pantethine and exposed to LACK or saline aerosol. After sacrifice of the animals, cells in the bronchoalveolar lavage were analyzed and inflammatory parameters were determined to evaluate inflammation seriousness.ResultsAs compared to untreated animals, pantethine-treated animals displayed a moderated response to the allergen, as documented by decreased infiltration of inflammatory cells (all types), in addition to reduced levels of lung Th2 cytokines and circulating LACK-specific IgE.ConclusionsThese data reveal the potential therapeutic importance of pantethine to moderate allergic asthma pathology. The compound has been previously shown to exert a broad range of protective activity in animals and in humans, with few or no adverse effects.

Progress in the understanding of the pathology of allergic asthma and the potential of fruit proanthocyanidins as modulators of airway inflammation.

Allergic asthma is a chronic inflammatory lung disease characterized by sensitization of the airways, and the development of immunoglobulin E antibodies, to benign antigens. The established pathophysiology of asthma includes recurrent lung epithelial inflammation, excessive mucus production, bronchial smooth muscle hyperreactivity, and chronic lung tissue remodeling, resulting in reversible airflow restriction. Immune cells, including eosinophils and the recently characterized type 2 innate lymphoid cells, infiltrate into the lung tissue as part of the inflammatory response in allergic asthma. It is well established that a diet high in fruits and vegetables results in a reduction of the risk of developing inflammatory diseases. Secondary plant metabolites, such as proanthocyanidins which are found in apples, blackcurrants, boysenberries, cranberries, and grapes, have shown promising results in reducing or preventing allergic asthma airway inflammation. Recent evidence has also highlighted the importance of microbiome-mediated metabolism of plant polyphenols in modulating the immune system. In this review, we will discuss advances in our understanding of the pathophysiology of allergic asthma, including the role of the microbiome in lung immune function, and how proanthocyanidins modulate the airway inflammation. We will highlight the potential of dietary proanthocyanidins to impact on allergic asthma and the immune system.

Calcitriol reduces eosinophil cytolysis and release of cytotoxic granules in vitro

Background Epidemiological studies show a strong correlation between vitamin D deficiency and asthma severity. Genetic studies have identified vitamin D receptor polymorphisms as a risk factor for asthma in diverse human populations. Calcitriol (1,25-dihydroxyvitamin D3), the physiologically active metabolite of mammalian vitamin D, is able to modulate receptor and cytokine expression as well as cell differentiation and maturation of various leukocytes in an anti-inflammatory manner. Despite the role of eosinophils in allergic asthma pathology, little is known about the effects of calcitriol on eosinophil biology. Calcitriol has a direct modulatory effect on eosinophil survival and effector functions in vitro.

Alveolar mast cells shift to an FcεRI-expressing phenotype in mild atopic asthma: a novel feature in allergic asthma pathology

A unique feature of alveolar mast cells is their low high-affinity IgE receptor (FcεRI) expression. Recent discoveries in uncontrolled asthma suggest that the appearance of FcεRI-expressing alveolar mast cells may be a novel disease-specific feature of allergic asthma. This study investigates whether increased FcεRI-expressing alveolar mast cells are present in patients with mild allergic asthma or even in non-asthmatic allergic rhinitis patients (AR) who have developed bronchial hyperactivity (BHR). Bronchial and alveolar tissues were obtained from healthy controls, AR patients with or without BHR, and AR patients with concurrent asthma. Samples were processed for immunohistochemical identification of MC(T) and MC(TC) and expression of FcεRI and surface-bound IgE. Bronchial mast cell expression of FcεRI was high in all groups. In contrast, in the alveolar tissue, the expression of FcεRI on mast cells was low in healthy controls and in the AR patient groups, whereas a high expression was present in AR patients with concurrent asthma (P = 0.006 compared to controls). The asthmatics had a 29-fold increase in numbers (P = 0.006) and a 19-fold increase in proportion (P = 0.007) of alveolar mast cells that expressed surface-bound IgE. The present data show that alveolar mast cells in patients with mild atopic asthma, but not atopic patients with AR, have turned into a highly FcεRI- and IgE-expressing phenotype. These data support the hypothesis that increased FcεRI expression on alveolar mast cells is a novel disease-specific feature of allergic asthma that is important for understanding asthma phenotypes and designing new therapeutic strategies.

Phthalate exposure and asthma in children

During the last decades more than 100 000 new chemicals have been introduced to the environment. Many of these new chemicals and many common consumer products that include these have been shown to be toxic in animal studies and an increasing body of evidence suggests that they are also impacting human health. Among the suspect chemicals, the endocrine disrupting chemicals (EDCs) are of particular concern. One such chemical group is the phthalates, used in soft poly vinyl chloride (PVC) material and in a huge number of consumer products. During the same period of time that the prevalence of these modern chemicals has increased, there has been a remarkable increase in several chronic illnesses, including asthma and allergy in children. In this article we outline the scientific knowledge on phthalate exposure for asthma and airway diseases in children by examining epidemiological and experimental peer review data for potential explanatory mechanisms. Epidemiological data point to a possible correlation between phthalate exposure and asthma and airway diseases in children. Experimental studies present support for an adjuvant effect on basic mechanisms in allergic sensitization by several phthalates. Despite variations in the experimental design and reported result in the individual studies, a majority of published reports have identified adjuvant effects on Th2 differentiation, production of Th2 cytokines and enhanced levels of Th2 promoted immunoglobulins (mainly IgG1 but also IgE) in mice. A limited amount of data do also suggest phthalate-induced enhancement of mast cell degranulation and eosinophilic infiltration which are important parts in the early inflammation phase. Thus, some of the early key mechanisms in the pathology of allergic asthma could possibly be targeted by phthalate exposure. But the important questions of clinical relevance of real life exposure and identification of molecular targets that can explain interactions largely remain to be answered.

SHIP1 Is a Repressor of Mast Cell Hyperplasia, Cytokine Production, and Allergic Inflammation In Vivo

SHIP1 inhibits immune receptor signaling through hydrolysis of the PI3K product phosphatidylinositol 3,4,5-trisphosphate, forming phosphatidylinositol 3,4-bisphosphate. In mast cells, SHIP1 represses FcepsilonRI- and cytokine-mediated activation in vitro, but little is known regarding the function of SHIP1 in mast cells in vivo or the susceptibility of Ship1(-/-) mice to mast cell-associated diseases. In this study, we found that Ship1(-/-) mice have systemic mast cell hyperplasia, increased serum levels of IL-6, TNF, and IL-5, and heightened anaphylactic response. Further, by reconstituting mast cell-deficient mice with Ship1(+/+) or Ship1(-/-) mast cells, we found that the above defects were due to loss of SHIP1 in mast cells. Additionally, we found that mice reconstituted with Ship1(-/-) mast cells suffered worse allergic asthma pathology than those reconstituted with Ship1(+/+) mast cells. In summary, our data show that SHIP1 represses allergic inflammation and mast cell hyperplasia in vivo and exerts these effects specifically in mast cells.

SHIP is a repressor of mast cell hyperplasia, cytokine production, and allergic inflammation in vivo (139.12)

Abstract Src homology 2-containing inositol 5'-phosphatase (SHIP) inhibits immune receptor signaling through hydrolysis of the phosphatidylinositol-3 kinase (PI3K) product PI-3,4,5-P3, forming PI-3,4-P2. SHIP represses FcεRI- and cytokine-mediated mast cell activation in vitro, but little is known regarding the function of SHIP in mast cells in vivo, or the susceptibility of Ship-/- mice to mast cell-associated diseases. In this study, we found that Ship-/- mice have systemic mast cell hyperplasia, increased serum levels of IL-6, TNF, and IL-5, and heightened anaphylactic response. Further, by reconstituting mast cell-deficient mice with Ship+/+ or Ship-/- mast cells, we found that the above defects were due to loss of SHIP in mast cells. Additionally, we found that loss of SHIP in mast cells alone resulted in increased allergic asthma pathology. In summary, our data show that SHIP represses allergic inflammation and mast cell hyperplasia in vivo, and that SHIP exerts these effects specifically in mast cells.

IL-13 is a novel therapeutic target in allergic asthma

Evaluation of: Bree A, Schlerman FJ, Wadanoli M et al. IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys. J. Allergy Clin. Immunol. 119, 1251–1257 (2007).There is abundant evidence supporting IL-13 as having a central role in the pathology of allergic asthma. IL-13 induces immunological responses relevant to allergic asthma and exerts effects on airway structural cells, leading to remodeling and enhanced contractility of airway smooth muscle. This paper evaluates the results from a recent preclinical study in cynomolgus monkeys, showing that treatment with an antibody to IL-13 significantly attenuates airway inflammation induced by segmental allergen challenge. Efficacy of anti-IL-13 in proof-of-concept human studies will be critical to evaluate the potential of this therapy for treatment of allergic asthma.