Characteristic Feature Of Asthma Research Articles

The Role of Airway Smooth Muscle during an Attack of Asthma SimulatedIn Vitro

Excessive narrowing of airways in response to contractile agonists is a characteristic feature of asthma. We hypothesized that airway smooth muscle (ASM) adaptation to short lengths could contribute to exaggerated airway narrowing during an acute attack of asthma by allowing the muscle to regain its ability to generate maximal force at a shortened length. To test this hypothesis we mimicked, in vitro, the sequence of contractile events that would occur during a spontaneous attack of asthma. Trachealis muscle was challenged with carbachol (300 nM, submaximal dose) and allowed to shorten to approximately half of its original length. After 30 min of adaptation at the shortened length in the presence of carbachol, muscle force, amount and rate of shortening in response to electrical stimulation were compared with corresponding values obtained from control experiments during which the ASM was not adapted to the short length. After adaptation at the shortened length the developed force, amount and rate of shortening increased by 1.93 +/- 0.08-, 1.57 +/- 0.12-, and 1.75 +/- 0.2-fold, respectively. Shortening of ASM in response to contractile agonists can lead to adaptation of the muscle to the shortened length that, in turn, can result in further shortening and the potential for airway closure.

Investigating the Role of Relaxin in the Regulation of Airway Fibrosis in Animal Models of Acute and Chronic Allergic Airway Disease

Airway remodeling is a characteristic feature of asthma that leads to chronic irreversible airway obstruction. Fibrosis in the basement membrane region is a hallmark of remodeling in asthma that is not found in other diseases. In the outlined studies, we investigated the relationship between relaxin and airway fibrosis in asthma using acute and chronic models of allergic airway disease. These studies confirm a critical role for relaxin, in the regulation of collagen deposition in the airway/lung in animal models of allergic airway disease.

Possible Involvement of CPI-17 in Augmented Bronchial Smooth Muscle Contraction in Antigen-Induced Airway Hyper-Responsive Rats

Airway hyper-responsiveness (AHR) associated with heightened airway resistance and inflammation is a characteristic feature of asthma. It has been demonstrated that contractile responsiveness and Ca(2+) sensitization to acetylcholine (ACh) in repeated antigen challenge-induced airway hyper-responsive bronchial preparation were significantly increased. The CPI-17 (PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa) is activated by protein kinase C and acts on a myosin light-chain phosphatase-specific target. The aim of the present study was to explore the role of CPI-17 in hyper-responsiveness of bronchial smooth muscle in antigen-induced AHR rats. In immunoblotting, the levels of expression of CPI-17 mRNA and protein were significantly increased in bronchus from rats that were repeatedly challenged with antigen. ACh-induced CPI-17 phosphorylation and translocation to membrane fraction were also significantly increased in bronchus from antigen-challenged rats. In conclusion, we suggest that augmented expression and activation of CPI-17 observed in the hyper-responsive bronchial smooth muscle might be responsible for the enhanced ACh-induced Ca(2+) sensitization of bronchial smooth muscle contraction associated with AHR.

Epithelial Expression of Profibrotic Mediators in a Model of Allergen-Induced Airway Remodeling

Airway remodeling, including subepithelial fibrosis, is a characteristic feature of asthma and likely contributes to the pathogenesis of airway hyperresponsiveness. We examined expression of genes related to airway wall fibrosis in a model of chronic allergen-induced airway dysfunction using laser capture microdissection and quantitative real-time PCR. BALB/c mice were sensitized and subjected to chronic ovalbumin exposure over a 12-wk period, after which they were rested and then harvested 2 and 8 wk after the last exposure. Chronic allergen-exposed mice had significantly increased indices of airway remodeling and airway hyperreactivity at all time points, although no difference in expression of fibrosis-related genes was found when mRNA extracted from whole lung was examined. In contrast, fibrosis-related gene expression was significantly upregulated in mRNA obtained from microdissected bronchial wall at 2 wk after chronic allergen exposure. In addition, when bronchial wall epithelium and smooth muscle were separately microdissected, gene expression of transforming growth factor-beta1 and plasminogen activating inhibitor-1 were significantly upregulated only in the airway epithelium. These data suggest that transforming growth factor-beta1 and other profibrotic mediators produced by airway wall, and specifically, airway epithelium, play an important role in the pathophysiology of airway remodeling.

Effect of Corticosteroids on Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease

Periodic exacerbations of disease severity, which may lead to hospitalization, are a characteristic feature of asthma and chronic obstructive pulmonary disease (COPD), becoming more prevalent as disease severity increases. Oral corticosteroids increase the rate of resolution of these episodes in both diseases. Inhaled corticosteroids are much less effective at conventional doses and are not recommended as a primary treatment for exacerbations of either disease. Maintenance therapy with inhaled corticosteroids significantly reduces the chance that a further exacerbation will occur in asthma. In general, increasing doses of inhaled corticosteroids are more effective than placebo therapy in preventing exacerbations, at least until patients become persistently symptomatic and regular users of inhaled corticosteroid therapy. Thereafter, the gains from doubling the dose of inhaled corticosteroid maintenance therapy are modest and generally inferior to those that result from adding other antiinflammatory or bronchodilator agents to the treatment regime. The reduction in the incidence of exacerbations with inhaled corticosteroids, compared with placebo, ranges from 15 to 20% in COPD versus almost 50% in severe asthma. However, given the impact of exacerbations on overall quality of life in COPD, even this modest reduction is likely to be clinically important.

PAR-2 et activation des cellules musculaires lisses bronchiques humaines

Bronchial hyperresponsiveness, airway inflammation involving mast cells and airway remodelling are characteristic features of asthma. Mast cells produce a significant amount of proteases, and the biological role of these enzymes is now being re-assessed owing to the recent identification of specific receptors, the so-called Proteinase Activated Receptors (PAR). Four types of PAR receptors have been described so far; all of them are coupled to G proteins. Mast cell tryptase activates type 2 PAR receptors (PAR-2) present on human airway smooth muscle cells, and this triggers calcium signalling in these cells, which leads to contraction and proliferation (airway remodelling). PAR-2 stimulation also triggers the cells to secrete cytokines such as TGF- β1, which can induce chemotaxis of mast cells. Thus, activation of PAR-2 on human airway smooth muscle cells by its physiological agonist, mast cell tryptase, produces smooth muscle contraction and proliferation, thereby enhancing airway inflammation, a characteristic feature of the pathophysiology of asthma.

An important role for relaxin-1 in the regulation of airway fibrosis and airway hyperresponsiveness in an animal model of asthma

Rationale Airway remodeling is a characteristic feature of asthma that leads to airway hyperresponsiveness (AHR) and irreversible airway obstruction. Collagen deposition in the subepithelial region is a hallmark of airway remodeling in asthma that does not occur in other airway disease. The factors regulating this collagen deposition have not been defined. The relative roles of airway remodeling and airway inflammation in the development of AHR also remain unclear. Furthermore, the specific contribution that individual components of remodeling make to AHR are not known. Method We examined the role of relaxin (a peptide hormone which stimulates collagen degradation) in the regulation of collagen deposition in an animal model of asthma using relaxin-deficient (RLX KO) mice. The relationship between airway remodeling, inflammation and AHR were also assessed. Results Both OVA treated RLX KO and OVA treated wild type (WT) mice developed marked airway inflammation. Lung collagen content was significantly increased in OVA RLX KO mice (p<0.05) with deposition predominantly in the airway subepithelial and adventitial regions. Importantly, unsensitized RLX KO mice with existing airway fibrosis demonstrated significantly increased AHR as compared to WT controls (p<0.05). Furthermore, in RLX KO mice, AHR was not modulated following OVA treatment, despite the development of airway inflammation. Conclusions These findings demonstrate a critical role for relaxin in the inhibition of lung collagen deposition during an allergic inflammatory response. Furthermore, they directly demonstrate that structural changes per se can lead to AHR independent of airway inflammation, while, existing airway fibrosis may protect against worsening of AHR associated with airway inflammation.

Ca 2+ sensors modulate asthmatic symptoms in an allergic model for asthma

We previously described two novel peptides, Ca 2+-like peptide (CALP) 1 and CALP2, which interact with Ca 2+-binding EF hand motifs, and therefore have the characteristics to define the role of the Ca 2+-sensing regulatory protein calmodulin in asthma. In the present study, the effects of the calcium-like peptides were investigated in an animal model for allergic asthma. For that purpose, sensitized guinea pigs were intratracheally pretreated with CALP1 or CALP2. Thirty minutes later, the animals were challenged with aerosolized ovalbumin. Acute bronchoconstriction was measured as well as characteristic features of asthma 6 and 24 hours (h) after challenge. Neither CALP1 nor CALP2 prevented the anaphylactic response elicited by ovalbumin challenge. However, CALP1 pretreatment attenuated the influx of inflammatory cells in the lungs 6 h after challenge. Furthermore, radical production by these cells was diminished both 6 and 24 h after challenge. Moreover, CALP1 completely inhibited airway hyperresponsiveness in vitro 24 h after challenge. We conclude that CALP1, as a selective calmodulin agonist, inhibits the development of asthmatic features probably via the attenuation of mast cell degranulation and radical production. Specific modulation of calmodulin activity might therefore be a potential new target for the treatment of allergic asthma.

Airway Hyperresponsiveness

Airway hyperresponsiveness is a characteristic feature of asthma and consists of an increased sensitivity of the airways to an inhaled constrictor agonist, a steeper slope of the dose-response curve, and a greater maximal response to the agonist. Measurements of airway responsiveness are useful in making a diagnosis of asthma, particularly in patients who have symptoms that are consistent with asthma and who have no evidence of airflow obstruction. These tests can be performed quickly, safely, and reproducibly. Certain inhaled stimuli, such as environmental allergens, increase airway inflammation and enhance airway hyperresponsiveness. These changes in airway hyperresponsiveness are of much smaller magnitude than those seen when asthmatic patients with persistent airway hyperresponsiveness are compared to healthy subjects. They are, however, similar to changes occurring in asthmatic patients that are associated with worsening asthma control. The mechanisms of the transient allergen-induced airway hyperresponsiveness are not likely to fully explain the underlying mechanisms of the persistent airway hyperresponsiveness in asthmatic patients.

Blood eosinophil and serum eosinophil cationic protein as a marker of bronchial hyperresponsiveness in children with suspected asthma

Purpose : Airway inflammation is considered to be a characteristic feature of asthma, and eosinophils are recognized as the most important inflammatory cells. This study aims to assess the importance of blood eosinophil count and serum eosinophil cationic protein(ECP) levels as a noninvasive marker of bronchial hyperresponsiveness(BHR) in children with suspected asthma. Methods : This study used data from 87 subjects with asthma-like symptoms(6-18 years old). The FEV1 and provocative concentration producing a 20% fall in FEV1(PC20) on methacholin inhalation challenge test were measured. Four groups were classified based on PC20[Group I : <2 mg/ mL; Group II : 2-8 mg/mL; Group III : 8-18 mg/mL; Group IV : (18 mg/mL], and blood eosinophil count and serum ECP levels were analyzed. In addition, subjects were classified based on the cutoff value of PC20(BHR positive group : <18 mg/mL; BHR negative group : (18 mg/mL). Then blood eosinophil count and serum ECP level were compared between these two groups. Results : Likelihood ratio test for trends revealed a significant association between the blood eosinophil count or serum ECP level, and the degree of BHR as measured by methacholine PC20. Blood eosinophil count or serum ECP level was significantly higher in the BHR(+) group than in the BHR(-) group. Blood eosinophil count had a positive correlation with serum ECP level. Conclusion : Blood eosinophil count and serum ECP level may be a useful non-invasive clinical marker of BHR in subjects with suspected asthma. This supports the hypothesis that BHR in asthma is a consequence of airway eosinophilic inflammation. (J Korean Pediatr Soc 2002;45: 1577-1584)

The association of sensitive systemic inflammation markers with bronchial asthma

Airway inflammation is a characteristic feature of bronchial asthma. Previous studies have shown an increased local inflammatory activity in the airway mucosa of asthma patients. To analyze the association of asthma with three sensitive markers of systemic inflammation, C-reactive protein, serum amyloid-A (SAA), and plasma fibrinogen. A cross-sectional, population-based study including 1,513 Finnish men aged 45 to 74 years, who participated in a chronic disease risk factor survey in 1997. Of the participating men, 97 were classified as asthma patients. The odds ratios of asthma were analyzed by quartile of each inflammation marker. In logistic regression models the age-adjusted odds ratios (second, third, and fourth quartile as compared with the first quartile) of asthma increased gradually with increasing quartile of C-reactive protein (1.28, 1.19, 1.96, P for trend = 0.039), SAA (1.20, 3.00, 3.49, P for trend < 0.001), and fibrinogen (1.22, 1.79, 3.16, P for trend < 0.001). The associations were independent of smoking. Further adjustment for waist-to-hip ratio, a marker of central obesity, and symptoms of chronic bronchitis weakened the observed association, but the increasing trend in the association of SAA and fibrinogen with asthma remained highly significant. Sensitive markers of systemic inflammation, particularly SAA and fibrinogen, were positively and significantly associated with asthma prevalence. These findings support the hypothesis that not only local, but also systemic, inflammation exist in bronchial asthma.

Treating the allergic patient: think globally, treat globally.

Treating the allergic patient: think globally, treat globally.

Proliferative effects of eosinophil lysates on cultured human airway smooth muscle cells.

The hypertrophy/hyperplasia of airway smooth muscle (ASM) cells is one of the characteristic features of bronchial asthma. This structural change leads to the thickening of airway walls resulting in the amplification of airway narrowing. However, the pathogenesis of this structural change has not yet been determined. Eosinophils, which play a pathogenic role in asthma, have been demonstrated to have proliferative effects on fibroblasts and vascular smooth muscle cells. We attempted to investigate the potential of eosinophils to induce the proliferation of ASM cells. We examined the effect of lysates of eosinophils purified from peripheral blood of healthy donors on cultured human ASM cell proliferation. Eosinophil lysates significantly induced ASM cell proliferation in time- and dose-dependent manners, reaching a maximum on day 6 at 50% of eosinophil lysates (6.0 +/- 0.7 x 104 [mean +/- SD] /well, n = 5 vs. 4.5 +/- 1.1 x 104/well, n = 5; P < 0.05). This proliferative activity was heat-sensitive and recovered in the soluble fraction of the eosinophil lysates. Furthermore, the molecular weight of the mitogenic activity in the soluble fraction was identified as lower than 10 kDa. The inhibitory activity to ASM cell proliferation was also found in the insoluble fraction of the lysates. These results indicate that circulating eosinophils store mitogenic activity for ASM cells, suggesting that eosinophils might contribute to the development of the hyperplasia of ASM cells in asthmatics through the release of the stored mitogenic activity upon stimulation at the site of inflammation.

Airway Hyperresponsiveness and Calcium Handling by Smooth Muscle: A “Deeper Look”

We propose that abnormal calcium handling by the airway smooth muscle may be an important determinant of airway hyperresponsiveness. The amplitude, frequency, or localization of Ca(2+) oscillations in the smooth muscle may determine the degree of airway sensitivity and reactivity, which are characteristic features of asthma.

Matrix metalloproteinases and their inhibitors in the nasal mucosa of patients with perennial allergic rhinitis

Background: Allergic rhinitis and asthma show many similarities in their epithelial and inflammatory responses to allergens. However, one notable difference is that disruption and desquamation of the epithelium is a characteristic feature of asthma, whereas in perennial allergic rhinitis the epithelium is intact and thickened. One reason for this might be differing expression of matrix metalloproteinases (MMPs) or their inhibitors (TIMPs). There are few published data on the presence of MMPs or TIMPs in the nasal mucosa in rhinitis. Objective: The purpose of this study was to investigate MMP and TIMP mRNA and protein in nasal mucosa from subjects with perennial allergic rhinitis and from nonrhinitic control subjects. Methods: Biopsy specimens of nasal mucosa were taken from 10 well-characterized subjects with perennial allergic rhinitis and 10 nonrhinitic control subjects. MMP and TIMP mRNA was quantified through use of competitive RT-PCR, and protein was detected by means of Western blotting and ELISA. Results: TIMP-1 mRNA and TIMP-2 mRNA were present in nasal samples, but there was no significant difference between the 2 groups. Only small amounts of MMP-1, -2, -3, and -9 mRNA were detected in the same samples. The corresponding proteins were detected by means of Western blotting. TIMP-1 protein and TIMP-2 protein were quantified in tissue homogenates; there was no significant difference between the 2 groups. Conclusion: Our studies have demonstrated the presence of large amounts of TIMP-1 and TIMP-2 mRNA and protein in nasal mucosa. There is no upregulation of MMPs or changes in TIMP expression in the nasal mucosa of patients with allergic rhinitis. (J Allergy Clin Immunol 2001;108:791-6.)

The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma.

Interleukin (IL)-4 and IL-13 are key proinflammatory cytokines in asthma. Studies in transgenic mice show that both cytokines cause inflammation, but only IL-13 causes subepithelial fibrosis, a characteristic feature of asthma. We compared the in vitro profibrogenic effects of IL-4 and IL-13 using bronchial fibroblasts from asthmatic subjects. In the presence of transforming growth factor (TGF)-beta the cells transformed into contractile myofibroblasts and expressed alpha-smooth muscle actin and procollagen I. IL-4 and IL-13 also stimulated proliferation, but were relatively ineffective in promoting myofibroblast transformation. TGF-beta was more potent than the cytokines in stimulating release of endothelin-1 and vascular endothelial growth factor, whereas IL-4 and IL-13 were more potent stimuli for eotaxin release. Although neither IL-4 nor IL-13 induced profibrotic responses, both cytokines caused a corticosteroid-insensitive stimulation of TGF-beta2 release from primary bronchial epithelial cells. These data indicate that epithelial activation by IL-13 or IL-4 plays a critical role in initiating remodeling through release of TGF-beta2. TGF-beta2 then activates the underlying myofibroblasts to secrete matrix proteins and smooth muscle and vascular mitogens to propagate remodeling changes into the submucosa. In contrast, direct activation of submucosal fibroblasts by IL-4 and IL-13 has a proinflammatory effect via eotaxin release and recruitment of eosinophils into the airways.

Allergic inflammation and airway smooth muscle function

It is widely accepted that airway smooth muscle (ASM) contraction plays a key role in asthmatic attacks. Whether abnormalities of contractility or autonomic regulation exist in the asthmatic ASM is still debated. Studies based on isometric contraction failed to show differences in the force-generation capability between asthmatic and normal ASM. Recent studies in vitro have shown that sensitized ASM: (1) shortens more and more rapidly than normal ASM; and (2) develops a myogenic response to stretching. The increased velocity of shortening may compromise in vivo the ability of tidal cycling to reduce airway tone, which would result in an enhanced response to bronchoconstrictor stimuli. The myogenic response may result in a sustained bronchospasm after a deep inhalation, a maneuver that in normal individuals causes bronchodilatation. Although there is no evidence that neural or humoral abnormalities in the autonomic regulation of ASM tone are central to the pathogenesis of bronchial asthma, recent data suggest that ASM receptor dysfunction may develop secondary to airway allergic response. It has been shown that exposure of passively sensitized human bronchi to allergens in vitro causes M 2- and β 2-receptor dysfunction. Impairment of pre-junctional M 2-autoreceptors may result in an enhancement of neurally mediated bronchoconstrictor responses, whereas β 2-receptor dysfunction may reduce the sensitivity to bronchodilator treatment. Airway inflammation, which is a characteristic feature of bronchial asthma, may alter both the contractile properties and the autonomic regulation of ASM. These changes may contribute to the severity of asthma, as they may cause an imbalance between factors favoring and opposing airway narrowing.

In vivo Effects of Apoptosis in Asthma Examined by a Murine Model

Background: One of the characteristic features of bronchial asthma is the accumulation of various inflammatory cells, predominantly eosinophils, at the subepithelial region beneath the basement membrane of the airway. Apoptosis is a form of physiological cell death, through which the cellular contents including biologically active substances are kept in the cell membrane and are removed without their harmful effects. So, attempts were made to clarify whether the induction of apoptosis is beneficial in asthma by using a murine model with ovalbumin (OA) as responsible allergen. Methods: A/J mice, which are genetically predisposed to be hyperresponsive to acetylcholine, were immunized with OA and alum, accompanied by OA inhalation for 2 weeks, during which some of the mice were also treated with either anti-Fas monoclonal antibody or sham control hamster IgG intranasally. Airway responsiveness to acetylcholine was then analyzed by measuring airway resistance with a body plethysmograph box. Apoptosis was assessed by propidium iodide and TUNEL staining. Results: Inhalation of OA increased both airway responsiveness to acetylcholine and the number of cells, mostly eosinophils, infiltrated into the airway. Administration of anti-Fas antibody induced apoptosis in the infiltrated eosinophils and abolished augmentation of airway hyperresponsiveness caused by OA inhalation. Conclusion: Induction of apoptosis in proinflammatory cells including eosinophils at the airway may have a beneficial effect on suppressing airway hyperresponsiveness.

Degranulation status of airway tissue eosinophils in mouse models of allergic airway inflammation.

Eosinophil degranulation is a characteristic feature of asthma and allergic rhinitis. However, degranulated eosinophils have not been convincingly demonstrated in the common mouse models of these airway diseases. This study uses eosinophil peroxidase (EPO) histochemistry and transmission electron microscopy (TEM) analysis to assess eosinophil degranulation in the airways of ovalbumin (OVA)-sensitized and challenged BALB/c and C57BL/6 mice. Using TEM we also examined mouse and human blood eosinophils after in vitro incubation with formyl-Met-Leu-Phe (fMLP) or phorbol myristate acetate (PMA). Although OVA exposure induced significant nasal and lung eosinophilia, we did not observe any of the known cellular processes by which eosinophils release their granule products, i.e., eosinophil cytolysis, piecemeal degranulation, and exocytosis. The occurrence of other allergen-induced degranulation events was ruled out because no difference in granule morphology was observed between lung-tissue eosinophils and blood or bone-marrow eosinophils from control animals. Accordingly, there was no detectable extracellular EPO in lung tissues of allergic mice. Similarly, mouse blood eosinophils remained nondegranulated in vitro in the presence of fMLP and PMA, whereas the same treatment of human eosinophils resulted in extensive degranulation. This investigation indicates that OVA-induced airway inflammation in the present mouse strains does not involve significant eosinophil degranulation. It is speculated that this dissimilarity from the human disease may be due to a fundamental difference in the regulation of mouse and human eosinophils.

Beta(2)-adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells.

1. Airway smooth muscle (ASM) is a potential source of multiple pro-inflammatory cytokines during airway inflammation. beta-Adrenoceptor agonist hyporesponsiveness is a characteristic feature of asthma, and interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha are implicated in its cause. Here, the capacity of beta-adrenoceptor agonists to prevent release of GM-CSF, RANTES, eotaxin and IL-8, elicited by IL-1 beta or TNF alpha, was examined in human ASM cells. 2. Isoprenaline (approximately EC(50) 150 nM), a non-selective beta-adrenoceptor agonist, and salbutamol ( approximately EC(50) 25 nM), a selective beta(2)-adrenoceptor agonist, attenuated release of GM-CSF, RANTES and eotaxin, but not IL-8 (EC(50) >1 microM). The maximum extent of attenuation was RANTES > or = eotaxin > GM-CSF >> IL-8, and was prevented by either propranolol (1 microM), a non-selective beta-adrenoceptor antagonist, or ICI 118511 (IC(50) 15 nM), a selective beta(2)-adrenoceptor antagonist. 3. The cyclic AMP-elevating agents, dibutyryl cyclic AMP ( approximately EC(50) 135 microM), forskolin ( approximately EC(50) 530 nM) and cholera toxin ( approximately EC(50) 575 pg ml(-1)) abolished IL-1 beta-induced release of GM-CSF, RANTES and eotaxin, but not IL-8. 4. IL-1 beta (1 ng ml(-1)) attenuated early increases (up to 1 h) in cyclic AMP formation induced by salbutamol (1 microM), but not by forskolin (10 microM). The cyclo-oxygenase inhibitor, indomethacin (1 microM) prevented later increases (3 - 12 h) in IL-1 beta-stimulated cyclic AMP content, but did not prevent the attenuation by salbutamol of IL-1 beta-induced cytokine release. 5. We conclude in human ASM cells that activation of beta(2)-adrenoceptors and generation of cyclic AMP is negatively-linked to the release, elicited by IL-1 beta or TNF alpha, of eosinophil-activating cytokines such as GM-CSF, RANTES and eotaxin, but not IL-8.