Treatment Of Human Asthma Research Articles

Anti-inflammatory and immunomodulatory properties of Mentha piperita green-formulated gold nanoparticles and its effect on ovalbumin-induced asthma and lung pathological changes in rats

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of Au nanoparticles by Mentha piperita as a natural reducing and stabilising agent in alkaline medium without using any toxic reducing agent. The biosynthesized Au NPs@Mentha piperita were characterised by advanced physicochemical techniques like ultraviolet-visible (UV-Vis), Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX), and X-ray Diffraction (XRD) study. It has been established that Au NPs@Mentha piperita have a spherical shape with a mean diameter from ∼10 nm. To survey the cytotoxicity effects of Au NPs@Mentha piperita, MTT assay was used on HUVEC cell line. To survey the antioxidant properties of Au NPs@Mentha piperita, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The Au NPs@Mentha piperita inhibited half of the DPPH molecules in the concentration of 113 µg/mL. In the in vivo, wistar rats were divided to four groups; non-sensitised, sensitised to ovalbumin, sensitised and treated with dexamethasone (1.25 μg/mL), and Au NPs@Mentha piperita (5 μg/mL) in drinking water for 21 days. The levels of total protein (TP), phospholipase A2 (PLA2), immunoglobulin E (IgE), IFN-γ/IL-4 ratio, interferon gamma (IFN-γ), and interleukin 4 (IL-4) in BALF, and lung pathological changes were examined. A significant increase in PLA2, IgE, IL-4, and TP levels, all lung pathological indices as well as significant decrease in IFN-γ/IL-4 ratio was seen in the asthmatic compared to the control rats. Treatment with Au NPs@Mentha piperita (5 μg/mL) resulted in decreased PLA2, IgE, IL-4, and TP levels, but increased IFN-γ/IL-4 ratio compared to untreated sensitised rats. The Au NPs@Mentha piperita significantly improved the pathological changes of sensitised rats. The improvement effects of higher concentrations of the Au NPs@Mentha piperita extract were significantly more than those of dexamethasone. The improvement effects of Au NPs@Mentha piperita on pathological changes, immunological and inflammatory markers in sensitised rats comparable or even more potent than dexamethasone suggests the therapeutic potential of the nanoparticle in asthma. After confirming these results in clinical trial studies, Au NPs@Mentha piperita can be used as a new drug for the treatment of asthma in humans.

Biochanin A Ameliorates Ovalbumin-induced Airway Inflammation through Peroxisome Proliferator-Activated Receptor-Gamma in a Mouse Model

Asthma is an inflammatory airway disease affecting most of the population in the world. The current medication for asthma relieves airway inflammation but it has serious adverse effects. Biochanin A (BCA), a phytoestrogen, is an active component present in red clover, alfalfa, soy having anti-oxidant and anti-inflammatory properties. BCA was identified as a natural activator of peroxisome proliferator-activated receptor-gamma (PPARγ). The study aims to evaluate the effects of BCA in ovalbumin (OVA)-induced murine model of asthma and to study the role of PPARγ. We found that BCA administration reduced the severity of murine allergic asthma as evidenced histologically, and measurement of allergen-specific IgE levels in serum as well as in BAL fluid. BCA also reversed the elevated levels of inflammatory cytokines, cell infiltration, protein leakage into the airways and expression of hemoxygenase-1 in OVA-induced lungs. Further, we confirmed that BCA mediated inhibitory effects are mediated through PPARγ as assessed by treatment with PPARγ antagonist GW9662. Our results suggest that BCA is efficacious in a preclinical model of asthma and may have the potential for the treatment of asthma in humans.

Assessment of the Therapeutic Effects of Fucoxanthin by Attenuating Inflammation in Ovalbumin-Induced Asthma in an Experimental Animal Model.

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.

The Prospects of an Active Vaccine Against Asthma Targeting IL-5.

Allergen-specific T helper type 2 (Th2) responses followed by eosinophilic inflammation of the lung are important causes of allergic asthma. Interleukin-5 (IL-5) is a master regulator of eosinophil differentiation as well as activation. Blocking IL-5 using monoclonal antibodies (mAbs) against IL-5 is a powerful way to improve asthmatic symptoms in patients with an eosinophilic component of the disease. We have previously shown that vaccination against IL-5 can abrogate eosinophilic inflammation of the lung in allergic mice. More recently, we have demonstrated that eosinophil-mediated skin disease in horses with insect bite hypersensitivity can be strongly reduced by vaccination against IL-5. Here we would like to propose the development of a similar vaccine for the treatment of asthma in humans.

HCLCA1 DNA Vaccine Suppresses Cell Hyperplasia and Mucin Expression of Goblet Cells in vitro

Background: Excessive airway mucus secretion is a remarkable trait of asthma. Mucus overproduction mainly resulted from an increase in goblet cell numbers, which causes considerable damage to health. However, effective therapeutic treatments are still lacking for mucus hypersecretion. Human calcium-activated chloride channel 1 (hCLCA1) has been identified to be predominantly responsible for mucus hypersecretion. Objectives: In this study, we investigated the effects of an hCLCA1 DNA vaccine on the control of mucus production and goblet cell proliferation using an in vitro model goblet cell line (NCI-H292). Methods: The effect of the hCLCA1 DNA vaccine on cell viability and proliferative activity of NCI-H292/hCLCA1 was analyzed by electron microscopy, MTT assay, and flow cytometry. Expression of mucins and MUC5AC, a major member of the mucin gene family in airway goblet cells, was assessed under hCLCA1 DNA vaccine challenges by periodic acid-Schiff staining, quantitative real-time PCR and Western blot, respectively, and the expression profile of granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine in airway inflammation, was also examined by real-time PCR and immunocytochemistry. Results: Results showed that hCLCA1 overexpression caused high cell proliferation and mucin expression, whereas the hCLCA1 DNA vaccine could effectively reverse these abnormal effects. In addition, GM-CSF expression was highly induced by hCLCA1 overexpression and efficiently suppressed by hCLCA1 DNA vaccine. Conclusions: These results illustrate that the hCLCA1 DNA vaccine effectively inhibits cell hyperplasia and mucin gene expression of goblet cells, suggesting that the hCLCA1 DNA vaccine has potential value in the treatment of human asthma.

Experimental research The effects of budesonide on angiogenesis in a murine asthma model

IntroductionThe aim of this study is to determine the effects and mechanisms of budesonide on angiogenesis in a murine asthma model.Material and methodsMurine asthma models were established and mice were divided into three groups: the model group (OVA-sensitized and challenged mice), the BUD group (budesonide-treated mice) and the PBS group (normal control mice). Mice in the BUD group were administered with inhaled budesonide (100 µg/kg) daily. The effects on airway inflammation, angiogenesis, expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were examined.ResultsAdministration of budesonide ameliorated allergic airway inflammation (2.90 ±0.18 vs. 4.80 ±0.20, p < 0.01) and significantly reduced the percentage vascularity (0.78 ±0.14 vs. 2.83 ±0.90, p < 0.01) compared with those in the asthmatic model mice. It also reduced the expression of HIF-1α (immunohistochemistry results: 71.70 ±1.40 vs. 89.60 ±0.79, p < 0.001; western blotting results: 0.88 ±0.41 vs. 0.97 ±0.47, p < 0.05), as well as that of VEGF (immunohistochemistry results: 26.30 ±1.03 vs. 93.30 ±1.54, p < 0.001; western blotting results: 1.12 ±0.22 vs. 2.08 ±0.30, p < 0.01). Percentage vascularity had positive correlation with both HIF-1α (r = 0.785, p < 0.01) and VEGF (r = 0.693, p < 0.01) expression. Furthermore, there is positive relationship between HIF-1α and VEGF expression (r = 0.641, p < 0.05).ConclusionsThe results demonstrate that budesonide has an important inhibitory effect on angiogenesis in asthma. Inhaled administration of budesonide achieved anti-angiogenic activity through inhibition of HIF-1α and VEGF expression. The results support a potential anti-remodeling role for budesonide in the treatment of human asthma.

Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi

Background Equine obstructive pulmonary disease, also known as heaves or recurrent airway obstruction (RAO) is a common equine pulmonary disease with some similarities to human asthma and COPD, which represents a major cause of morbidity and loss of lung performance. Salbutamol has been widely used for the treatment of human airway diseases and has usually been prepared as the racemic form of the drug. However, recently the R-enantiomer of salbutamol has been introduced into clinical practice in the treatment of asthma in humans and this has been suggested to be an improvement on the racemic form of the drug; therefore thus the S-enantiomer has been demonstrated to have adverse effects in the lung and thus using the R-enantiomer may improve the therapeutic ratio. However, little is known about the properties of the R- and S-enantiomers of salbutamol in equine airways and the present study has evaluated the relaxant effects of racemic β 2-agonists in comparison with the R- and S-enantiomers in isolated equine isolated bronchi, as well as the bronchoprotective effects of these drugs on cholinergic and histaminergic pathway. Methods We have studied the effects of the R- and S-enantiomers of salbutamol on bronchi isolated from RAO-affected or unaffected horses. The first study assayed the relaxant effects of R- and S-salbutamol on isolated bronchial rings contracted with carbachol or histamine at a sub-maximal concentration (EC70). A second study evaluated the effects of R- and S-salbutamol on semi-logarithmic cumulative concentration-response curves induced by carbachol or histamine. Specific software was used to calculate statistical significance and the appropriate sigmoidal curve-fitting model. Results Neither enantiomers of salbutamol caused a relaxant effect on the sub-maximal plateau contractile effects of carbachol; in fact, both R- and S-salbutamol induced a slight, but significant contraction ( P ≤ 0.05) compared to the controls. In contrast, R-salbutamol induced a significant relaxation of bronchi pre-contracted with histamine (RAO-unaffected: 92.06% ± 2.00; RAO-affected 100.20 ± 3.99; P ≤ 0.01). S-salbutamol induced a weak relaxation (RAO-unaffected: 15.81% ± 5.65; RAO-affected 12.36 ± 5.15) when compared to that induced by papaverine. The incubation with either R- or S-salbutamol shifted rightward ( P ≤ 0.001) the carbachol contraction curve in RAO-unaffected bronchi, but not in RAO-affected bronchi, compared to control tissues. R-salbutamol induced a reduction in E max values (C: 9.07gr ± 0.68; R-salb.: 6.36gr ± 0.21; P ≤ 0.01) in normal bronchi. On the contrary it reduced the histamine potency in RAO-affected bronchi (EC50 7.10 μM ± 0.35, P < 0.001). The incubation with S-salbutamol shifted leftward the histamine concentration curve in both normal bronchi (C: 7.00 μM ± 0.29; S-salb.: 2.25 μM ± 0.19; P ≤ 0.001) and bronchi from RAO-affected horses (C: 2.80 μM ± 0.26; S-salb.: 1.50 μM ± 0.80; P ≤ 0.05). Conclusion Our studies have demonstrated that S-salbutamol elicited a modest increase in contraction of equine airway smooth muscle induced by carbachol and induced a significant hyperresponsiveness to histamine. These results confirm the ability of the S-enantiomer of salbutamol to potentiate the contractile effect of certain spasmogens on airway smooth muscle. Such an adverse effect would be determined in the airways of horses with RAO and suggest that if salbutamol is to be used in the treatment of symptoms of RAO in horses, the R-enantiomer, rather than the racemic mixture should be considered.

Iloprost has potent anti‐inflammatory properties on human monocyte‐derived dendritic cells

The stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs). The aim of the current study was to investigate the biological activity of iloprost on human monocyte-derived DCs. I prostanoid (IP) receptor expression was analysed by RT-PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co-culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry. Human monocyte-derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF-alpha, IL-6, IL-8 and IL-12p70 in mDCs, while it enhanced IL-10 production. Changes in cytokine secretion were paralleled by an altered T-cell priming capacity of DCs: in co-culture experiments of iloprost-treated mDC and naïve CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL-10 production. Additionally, iloprost inhibited the MIP-3beta-induced migration of mDCs. In summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans.

Eicosanoids in Asthma, Allergic Inflammation, and Host Defense

Eicosanoids are diverse mediators of inflammation that derive from a single cell membrane phospholipid-associated precursor, arachidonic acid. This precursor is metabolized to several groups of lipid mediators, including (but not limited to) prostaglandins, leukotrienes, and lipoxins, in a tightly regulated, coordinated, cell- and context-specific manner. Each mediator serves regulatory and homeostatic functions in the onset and resolution of inflammation, immune responses, and tissue repair. The cloning of biosynthetic enzymes and G protein-coupled receptors for each of these mediators, the development of transgenic mice deficient in these molecules, and the availability of selective antagonists have permitted studies that have rapidly expanded our understanding of the scope of biologic functions for these mediators, with potential ramifications for the pathogenesis and treatment of human asthma. This review summarizes these findings and reviews the data from both mouse and human studies pertinent to the pathobiologic role of each mediator.

Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease

Objective Bromelain, a clinically used pineapple extract and natural product, has reported anti-inflammatory and immunomodulatory activities. The purpose of this study was to determine the effect of bromelain treatment in an ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). Methods To establish AAD, mice were sensitized with intraperitoneal (i.p.) OVA/alum and challenged with daily OVA aerosols. Mice were treated i.p. with either saline, 2 or 6 mg/kg bromelain, twice daily for four consecutive days. Bronchoalveolar lavage leukocytes and cytokines, lung histology, airway hyperresponsiveness, and lymphocyte populations via flow cytometry were compared between groups. Results Bromelain treatment of AAD mice resulted in reduced total BAL leukocytes, eosinophils, CD4 + and CD8 + T lymphocytes, CD4 +/CD8 + T cell ratio, and IL-13. Conclusion Bromelain attenuated development of AAD while altering CD4 + to CD8 + T lymphocyte populations. The reduction in AAD outcomes suggests that bromelain may have similar effects in the treatment of human asthma and hypersensitivity disorders.

Novel immunomodulatory oligonucleotides prevent development of allergic airway inflammation and airway hyperresponsiveness in asthma

Oligodeoxynucleotides containing unmethylated CpG motifs (CpG oligos) have been shown to prevent development of allergic airway inflammation and airway hyperresponsiveness (AHR) in mouse models of asthma. Recently, we reported immunomodulatory oligonucleotides (IMOs) containing novel structures (immunomers) and synthetic immunostimulatory CpR (R=2′-deoxy-7-deazguanosine) motifs show potent stimulatory activity with distinct cytokine secretion profiles. Since type 2 T cells predominate in asthma and increase in type 1 cells can prevent the differentiation of naı̈ve T lymphocytes to a type 2 phenotype, we hypothesized that IMOs can prevent the development of allergic airway inflammation and AHR in the ovalbumin (OVA)-sensitized and challenged mouse model. We found that co-administration of novel IMOs during OVA-sensitization abrogated both early and late allergic responses (LARs). AHR to methacholine was also blocked with IMO treatment. Analysis of bronchoalveolar lavage (BAL) fluid of mice treated with IMOs demonstrated complete reduction in eosinophils, with concomitant decreases in both serum and BAL fluid IL-4, IL-5, and IL-6 levels. In addition, there was a significant reduction in serum IL-10 levels. IMOs, in general, significantly attenuated the rise in serum IgE levels. In comparison, IMOs showed a significantly more potent effect on early and late allergic response than a conventional CpG oligo in this model. These data suggest that the treatment with these novel IMOs prevents OVA-induced allergic airway inflammation and AHR in asthma in the mouse and may provide a useful agent in the treatment of human asthma.

Airway hyperresponsiveness: a story of mice and men and cytokines.

Bronchial hyperresponsiveness (BHR) is an essential part of the definition of asthma. Although our understanding of the allergic inflammatory and immunologic mechanisms of asthma have markedly increased, the mechanism of BHR remains to be elucidated. Increased BHR is associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain occupational chemicals. An important research use of determining the degree of BHR to direct and indirect challenge is to determine the efficacy of pharmacologic and immunodulatory agents. Beta-adrenergic agents inhibit BHR and certain genetic polymorphisms of the beta-adrenergic receptor are associated with increased BHR. When beta-adrenergic receptors are blocked, sensitivity to allergens is markedly increased in patients with asthma and animal models of asthma. Allergen challenge and clinical asthma are associated with synthesis and release of pro-inflammatory cytokines such as IL-1 and TNF-alpha which have been shown to decrease the response to beta-agonists and increased the reactivity to methacholine and the airways neutrophils and alveolar macrophages. The Th2 cytokine IL-13 is increased in the airways of asthmatics and increases BHR in normal unsensitized animals. The mechanisms of this effect of IL-13 are being intensively investigated. Our group has shown that IL-13 induced BHR persisted for at least 7 days and the soluble receptor IL-13R2alpha protected against their BHR. Other investigators have demonstrated that IL-13 is necessary and sufficient for the induction of BHR and that eosinophilic airway inflammation in the absence of IL-13 fails to induce BHR. These studies indicate that treatment of human asthma with antagonists of IL-13 may be very effective.

Detection of inhaled salbutamol in equine urine by ELISA and GC/MS2.

Salbutamol is a beta-adrenergic agonist that is used in the treatment of asthma in humans and chronic obstructive pulmonary disease in horses. Because of its stimulating and growth promoting properties, it is prohibited by horse racing authorities. Recently a number of adapters (eg Equinehaler) have been designed, allowing the use of metered dose inhalers (MDI) approved for human use. However, information on detection times of salbutamol after administration of salbutamol in therapeutic doses by inhalation is lacking. In this study, 2 mg salbutamol (Ventolin) was administered to four standardbred mares via an MDI with an Equinehaler and urine was collected during 48 h. Quantification of salbutamol in horse urine was done via an overnight beta-agonist ELISA kit. Salbutamol was detected between 1 and 48 h post-administration. Relatively large interindividual variations in the total amount excreted during the first 12 h were noticed. The maximum urinary concentrations varied between 4.6 and 8.1 ng/mL. The total amount excreted within the first 12 h varied between 0.2 and 0.7% of the administered dose. For confirmatory analysis in doping control, a GC/MS(2) method was developed and validated. Analysis was performed on an ion trap instrument after solid phase extraction. The limit of detection was 0.25 ng/mL and was lower than in previously reported methods in human urine.

Amb a 1–linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma

Background: Recently, it has been demonstrated that immunostimulatory DNA sequences (ISS) containing CpG motifs prevent the development of allergic airway responses in murine models of disease. However, few studies have addressed the issue of whether these agents will reverse established Tm H2-driven allergic airway responses. Objective: The aim of this study was to determine whether intradermal delivery of an immunogenic protein of ragweed pollen linked to an immunostimulatory DNA sequence could reverse an established allergic response in the mouse lung. Methods: Mice sensitized and challenged with ragweed pollen extract were treated intradermally twice at 1-week intervals with an ISS chemically linked to Amb a 1 (Amb a 1-ISS). One week after the Amb a 1-ISS treatment, mice were rechallenged intratracheally with ragweed extract, and airway responses were assessed. Results: Amb a 1-ISS treatment of ragweed-sensitized and ragweed-challenged mice significantly reversed allergen-induced airway hyperresponsiveness and suppressed the total number of eosinophils in bronchoalveolar lavage fluid. The inhibitory effect of Amb a 1-ISS was associated with a marked increase in IFN-γ levels by Amb a 1-stimulated splenocytes and a shift in the antibody profile from a T H2-directed IgG1 response to a T H1-directed IgG2a response. Interestingly, the inhibitory effect of Amb a 1-ISS on allergen-driven airway hyperresponsiveness was independent of suppression of T H2 cytokine production. Conclusion: These results demonstrate that intradermal delivery of allergen-specific DNA conjugates can reverse established allergic responses in the murine lung, supporting their potential use in the treatment of human asthma. (J Allergy Clin Immunol 2002;109:455-62.)

Flt3 ligand: a novel cytokine prevents allergic asthma in a mouse model

Flt-3 ligand (FL), a recently described growth factor affecting early hematopoietic progenitor cells, can also support the expansion of dendritic cells secreting IL-12. Since type 2 T cells predominate in asthma and IL-12 prevents the differentiation of naive T lymphocytes to a type 2 phenotype, we hypothesized that FL could prevent the development of asthma-like conditions in the ovalbumin mouse model. We found that co-administration of FL during ovalbumin sensitization abrogated late allergic responses, but had no effect on early allergic responses. Airway hyperresponsiveness to methacholine was also blocked by FL treatment. Analysis of bronchoalveolar lavage (BAL) fluid demonstrated a significant reduction in eosinophils, with concomitant decreases in IL-5 and increases in IFN-γ levels. However, there was no change in BAL fluid IL-4 and serum IgE levels. These data suggest that FL treatment prevents ovalbumin-induced asthma in the mouse and may provide a useful adjuvant in the treatment of human asthma.

Critical role for IL-13 in the development of allergen-induced airway hyperreactivity.

Airway hyperresponsiveness to a variety of specific and nonspecific stimuli is a cardinal feature of asthma, which affects nearly 10% of the population in industrialized countries. Eosinophilic pulmonary inflammation, eosinophil-derived products, as well as Th2 cytokines IL-13, IL-4, and IL-5, have been associated with the development of airway hyperreactivity (AHR), but the specific immunological basis underlying the development of AHR remains controversial. Herein we show that mice with targeted deletion of IL-13 failed to develop allergen-induced AHR, despite the presence of vigorous Th2-biased, eosinophilic pulmonary inflammation. However, AHR was restored in IL-13(-/-) mice by the administration of recombinant IL-13. Moreover, adoptive transfer of OVA-specific Th2 cells generated from TCR-transgenic IL-13(-/-) mice failed to induce AHR in recipient SCID mice, although such IL-13(-/-) Th2 cells produced high levels of IL-4 and IL-5 and induced significant airway inflammation. These studies definitively demonstrate that IL-13 is necessary and sufficient for the induction of AHR and that eosinophilic airway inflammation in the absence of IL-13 is inadequate for the induction of AHR. Therefore, treatment of human asthma with antagonists of IL-13 may be very effective.

Th2 cytokines and asthma — The role of interleukin-5 in allergic eosinophilic disease

Interleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, interleukin-5 is a very selective cytokine as a result of the restricted expression of the interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of interleukin-5 is a viable treatment. The present review addresses the data that relate interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-interleukin-5 monoclonal antibodies for the treatment of asthma in humans.

Chlorphenesin: A New Inhibitor of IgE-Mediated Histamine Release

Abstract Several drugs have recently been shown to be active in inhibiting the antigenically induced in vitro release of compounds thought to be involved in anaphylactic reactions. These compounds offer interesting tools with which to study the mechanism of the reactions of immediate hypersensitivity as well as having the potential for therapeutic use in man. Of the drugs already in use in man diethylcarbamazine (Hetrazan), an antifilarial agent, inhibits the release of the slow reacting substance of anaphylaxis (SRS-A) from rat peritoneal leukocytes (1) while disodium chromoglycate (Intal) inhibits the release of histamine from rat mast cells in vivo (2). The latter, however, does not inhibit in vitro histamine release from human leukocytes (L. M. Lichtenstein, unpublished). Both of these drugs are currently being studied for their usefulness in the treatment of human asthma (3, 4). Recently, drugs of the catecholamine and methylxanthine series were shown to inhibit the release of histamine from human leukocytes: evidence was presented to suggest that they operated through the cyclic 3′5′ AMP system (5, 6).