Alveolar macrophage accessory cell function in bronchial asthma.

The capacity of peripheral blood monocytes and alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) to present recall antigens, namely, tuberculin purified protein derivative (PPD) or streptokinase-streptodornase (SKSD), to highly purified autologous T-cells has been studied in 11 asthmatic and 11 healthy, nonatopic normal subjects. In the asthmatic group, AM accessory cell function was variable, and most subjects were unable to present either recall antigen as effectively as blood monocytes, although one asthmatic subject demonstrated larger proliferative responses than blood monocytes for both antigens. AM accessory cell activity was not antigen-specific, and there was a correlation between accessory cell efficacy for the two antigens (r = 0.92; confidence interval, 0.53 to 0.98). Furthermore, a correlation existed between the percentage lymphocyte count in the BAL fluid and the ratio of macrophage to monocyte antigen-presenting capability for both PPD (r = 0.92; 95% confidence interval, 0.83 to 0.99) and SKSD (r = 0.90; 95% confidence interval, 0.45 to 0.98). In the normal subjects, AM were also unable to act effectively as accessory cells for the presentation of PPD and SKSD in the majority of subjects. No correlation existed between the percentage lymphocytes in BAL fluid and the ratio of AM to monocyte accessory cell function. These results suggest an association between AM accessory function and the presence of BAL lymphocytes in bronchial asthma.     

Different IL-5 and IFN-γ Production from Peripheral Blood T-Cell Subsets in Atopic and Nonatopic Asthmatic Children

Defective Th1 and enhanced Th2-type cytokine responses have been implicated in the development of atopic disease. However, the immunopathology of nonatopic asthma, especially in children, remains unclear, and there have been few studies to compare the cytokine profile in peripheral blood T-cell subsets between atopic and nonatopic asthmatic children. To document whether atopic asthmatic children have a cytokine imbalance and to compare the cytokine profile between atopic and nonatopic asthmatic children, we investigated the interleukin (IL)-5-producing and interferon (IFN)-γ-producing T-cell subsets from peripheral blood mononuclear cells (PBMC). The percentages of IFN-γ-producing CD4⁺ and CD8⁺ T cells from atopic asthmatic children were decreased, but those in nonatopic asthmatic children were not decreased. In both groups of asthmatic children, the percentages of IFN-γ-producing CD4⁺ T cells were inversely correlated with the peripheral blood eosinophils and had a significant correlation with airway responsiveness (PC₂₀). Thus, we found that the mechanism underlying allergic inflammation of nonatopic asthma is not simple a Th1/Th2 cytokine imbalance. Considering the inverse relationship between IFN-γ-producing CD4⁺ T cells and eosinophilia or airway hyperresponsiveness, IFN-γ from CD4⁺ T cells may play an important role in allergic inflammation and airway hyperresponsiveness in asthmatic children.     

Different IL‐5 and IFN‐γ Production from Peripheral Blood T‐Cell Subsets in Atopic and Nonatopic Asthmatic Children

Defective Th1 and enhanced Th2‐type cytokine responses have been implicated in the development of atopic disease. However, the immunopathology of nonatopic asthma, especially in children, remains unclear, and there have been few studies to compare the cytokine profile in peripheral blood T‐cell subsets between atopic and nonatopic asthmatic children. To document whether atopic asthmatic children have a cytokine imbalance and to compare the cytokine profile between atopic and nonatopic asthmatic children, we investigated the interleukin (IL)‐5‐producing and interferon (IFN)‐γ‐producing T‐cell subsets from peripheral blood mononuclear cells (PBMC). The percentages of IFN‐γ‐producing CD4⁺ and CD8⁺ T cells from atopic asthmatic children were decreased, but those in nonatopic asthmatic children were not decreased. In both groups of asthmatic children, the percentages of IFN‐γ‐producing CD4⁺ T cells were inversely correlated with the peripheral blood eosinophils and had a significant correlation with airway responsiveness (PC₂₀). Thus, we found that the mechanism underlying allergic inflammation of nonatopic asthma is not simple a Th1/Th2 cytokine imbalance. Considering the inverse relationship between IFN‐γ‐producing CD4⁺ T cells and eosinophilia or airway hyperresponsiveness, IFN‐γ from CD4⁺ T cells may play an important role in allergic inflammation and airway hyperresponsiveness in asthmatic children.     

TH1 and TH2 Cytokine Production Among Asthmatic Children After Immunotherapy

Allergen immunotherapy results in a number of changes in clinical and immunological parameters. To study the kinetic influence of immunotherapy on cytokine production, we evaluated the ratios of Th1/Th2 for patients receiving mite-extract immunotherapy with 3-month intervals. Changes in Th1/Th2 ratio were calculated based on the intracellular cytokine and surface CD4 staining of peripheral blood mononuclear cells (PBMC). No significantly different Th1/Th2 ratios were detected after immunotherapy, although ratios were lower for asthmatic children when compared with normal controls. Cytokine production was also determined on supernatants from mite- or mitogen-activated PBMC cells. A significantly increased production of all cytokines was detected from activated PBMC from patients after immunotherapy. Thus hyposensitization with mite extract for 1 year might improve the cytokine production capacity of asthma patients' PBMC.     

TH1 and TH2 Cytokine Production Among Asthmatic Children After Immunotherapy

Allergen immunotherapy results in a number of changes in clinical and immunological parameters. To study the kinetic influence of immunotherapy on cytokine production, we evaluated the ratios of Th1/Th2 for patients receiving mite-extract immunotherapy with 3-month intervals. Changes in Th1/Th2 ratio were calculated based on the intracellular cytokine and surface CD4 staining of peripheral blood mononuclear cells (PBMC). No significantly different Th1/Th2 ratios were detected after immunotherapy, although ratios were lower for asthmatic children when compared with normal controls. Cytokine production was also determined on supernatants from mite- or mitogen-activated PBMC cells. A significantly increased production of all cytokines was detected from activated PBMC from patients after immunotherapy. Thus hyposensitization with mite extract for 1 year might improve the cytokine production capacity of asthma patients' PBMC.     

Infection of human monocytes with HIV-1Ba-L. Effect on accessory cell function for T-cell proliferation in vitro

Major laboratory manifestations of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) include altered levels of circulating CD4+ lymphocytes and decreased in vitro T-cell mitogenic responses. Since T-cell proliferation is regulated by monocytes (M phi), studies were undertaken to determine whether defective M phi function contributes to these poor mitogenic responses. M phi were isolated from peripheral blood mononuclear cells (PBMC) of normal donors by adherence to plastic. After 5 days in culture, the adherent cells were inoculated with the HIV-1 M phi-tropic strain, Ba-L. Under these conditions HIV infection in M phi can be detected 5-7 days after inoculation. Ten to fourteen days postinoculation, the adherent cells were harvested with lidocaine and cocultured with fresh autologous T cells and T-cell mitogens in a 3-day assay. We found decreased proliferative anti-CD3 responses to Leu4 and OKT3 and variable responses to concanavalin A (Con A) by T cells cultured with HIV-infected monocytes compared with T cells cultured with uninfected M phi. Supernatants from HIV-infected M phi cultures decreased proliferative responses of normal PBMC to anti-CD3 monoclonal antibodies. Heat-activated supernatants had the same effect. Inhibitors of HIV binding did not restore proliferative responses of HIV-infected cultures to normal levels. These results indicate that HIV infection of M phi causes the release of soluble factor(s) that suppress anti-CD3-induced T-cell proliferative responses.     

Relationship of Adipokines with Immune Response and Lung Function in Obese Asthmatic and Non-Asthmatic Women

Background. Obesity is a risk factor for asthma. Studies in mice suggest that the adipokines leptin and adiponectin affect asthmatic responses. The purpose of this study was to determine if adipokines associated with obesity are (1) altered in obese women with asthma compared to controls and (2) associated with increased cytokines and chemokines involved in allergic inflammation. Methods. We performed a cross-sectional study of asthmatic and non-asthmatic obese premenopausal women. Participants answered questionnaires and performed lung function tests. Serum and peripheral blood mononuclear cells (PBMCs) were collected for analysis of cytokines and adipokines. Results. A total of 22 asthmatic (mean body mass index 40.0 ± 5.1 kg/m²) and 20 non-asthmatic women (mean body mass index 41.3 ± 5.6 kg/m²) participated. We found no difference in serum adipokine concentrations between asthmatics and non-asthmatics. Serum adiponectin correlated positively with PBMC eotaxin (r_s = 0.55, p = .0003) and RANTES (regulated upon activation, normal T-cell expressed, and secreted) (r_s = 0.36, p = .03), whereas serum leptin correlated negatively with PBMC eotaxin (r_s = ?0.34, p = .04). There was a negative correlation between serum adiponectin and PBMC interferon-γ (r_s = ?0.41, p = .01). Conclusions. Perturbations of adipokines that occur in obesity were correlated with decreased cytokine production typically associated with allergic responses in PBMC of obese premenopausal women. This study suggests that although obese asthmatics may have elements of Th2-mediated inflammation, adipokine derangements in obesity are associated with Th1 rather than Th2 bias. Obesity has complex effects on allergic inflammation and is likely to be important modifier of the pathogenesis of airway disease in asthma.     

Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation

The local mechanisms that result in the cellular inflammation and bronchial airway hyperreactivity that characterize allergic bronchial asthma are poorly defined. In order to study these processes, we developed a method for local allergen challenge using a fiberoptic bronchoscope and direct observation and bronchoalveolar lavage (BAL) to assess the airway responses to allergen. In these studies, 11 allergic asthmatics (all of whom had previously demonstrated a late-phase asthmatic response to aeroallergen challenge) and 6 healthy, asymptomatic subjects volunteered to undergo bronchoalveolar lavage after local airway challenge via a bronchoscope wedged into subsegmental airways. These studies revealed that asthmatic airways respond to allergen with an immediate pallor followed by reactive hyperemia, edema, and bronchial narrowing. This site and a control site were relavaged at 48 or 96 h after the immediate response. Neutrophils and eosinophils increased significantly at 48 h after challenge, as did helper T-lymphocytes. Characteristically, at 96 h, neutrophil counts returned to normal values, whereas eosinophiles and helper T-cells remained elevated. Peroxidase-staining cells were also elevated at 48 h after local allergen challenge. Electron microscopy revealed degranulation of mast cells and eosinophils, both immediately and later (48 and 96 h) after local allergen challenge. Macrophages were highly activated and had phagocytized, partially intact granules from both eosinophils and mast cells. There was a significant correlation (p less than 0.001) between the concentration of allergen required to produce a visible airway response and a positive end-point skin titration in the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phenotypic analysis of alveolar macrophages and lymphocytes following allergen inhalation by atopic subjects with mild asthma

BACKGROUND: The airway inflammation associated with allergic asthma is initiated through a complex interaction of antigen-presenting cells (APC) and T lymphocytes resulting in the release of a cascade of cytokines regulating the progress of the allergic inflammatory response. In the present study the state of alveolar macrophage (AM) and T cell activation was investigated following induction of allergic airway inflammation in individuals with atopic asthma. METHODS: Eleven individuals with mild, atopic asthma received cumulated allergen inhalations. Before and one day after challenge, bronchoalveolar lavage (BAL) was performed, and peripheral blood samples obtained. Ten healthy individuals served as controls. The expression of cell surface markers by BAL fluid AMs and T cells, and by blood T cells, was investigated by flow cytometry. RESULTS: All patients developed early asthmatic reactions (EAR) with increased numbers of eosinophils and mast cells in BAL fluid following allergen challenge. After allergen challenge, patients had relatively fewer pulmonary CD4+ T cells expressing CD69 and HLA class II and also relatively fewer pulmonary CD8+ T cells expressing HLA class II, compared to before challenge. An increased quantitative expression of CD14 and CD86 was seen within the AM population following allergen challenge. CONCLUSION: The results indicate a recruitment of non-activated, immature macrophages and CD4+ T cells to the airways as well as an altered phenotype pattern within the AM population following induction of allergic airway inflammation by allergen inhalation challenge in asthma.     

Immunological Changes After Hyposensitization in House-Dust-Sensitive Asthmatic Children: A Review

Patients with allergic diseases are characterized by the presence of elevated total serum IgE and specific IgE antibodies against a variety of environmental allergens. To explore the causes for augmented IgE antibody production and the working mechanisms of hyposensitization (HS), a series of studies has been conducted on house-dust-sensitive, newly diagnosed, and hyposensitized asthmatic children and normals.

The specific IgE and IgG antibodies were measured by radioallergosorbent test; the lymphoproliferative capability was measured by ³H-thymidine incorporation; the allergen-specific suppressor activity was determined by the extent of house-dust-activated, interleukin-2 (IL-2)-expanded lymphocytes to suppress the allergen-induced proliferation of autologous mononuclear cells (MNC); and IL-2 was produced by stimulating MNC with allergen or phytohemagglutinin (PHA) and quantitated by its capability to support the proliferation of mouse IL-2-dependent cytotoxic T-cell line.

The results showed: 1) HS was effective in 90% of patients in terms of decreased attacks and medication taken; 2) the patients were defective in suppressor T-cell function for IgE production; 3) HS was able to restore the regulatory T-cell function and increase the production of IgG-blocking antibody; and 4) IL-2 production may be used as an indicator for initiation and discontinuation of HS.

Therefore, hyposensitization is an effective and specific treatment for allergic bronchial asthma and can partially correct an immunoregulatory aberration in atopic individuals.     

Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation.

We have previously demonstrated the production of tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) by alveolar macrophages (AM) from allergic asthmatics developing a late asthmatic reaction after bronchial allergen challenge. In order to explain the modalities of this monokine synthesis, we tested in vitro the effect of an IgE-dependent stimulation on blood monocytes (BM) and AM from control and asthmatic subjects. TNF and IL-6 secretions were evaluated in 24-h supernatants by radioimmunoassay and by the 7TD1 cell proliferation test, respectively. AM from allergic asthmatics secreted spontaneously higher concentrations of TNF and IL-6 than did BM or AM from control subjects. BM from asthmatics also produced spontaneously increased levels of TNF, but at a lesser degree than did AM. The addition of anti-IgE induced a significant increase of TNF and IL-6 secretions by mononuclear phagocytes from control subjects only after previous sensitization with IgE-rich medium. In contrast, the direct stimulation by allergen or anti-IgE of AM and BM from asthmatics enhanced significantly the production of TNF and IL-6 when compared with cells cultured in medium alone. In these conditions, IgE-dependent activation of cells from allergic asthmatics compared with those from control subjects increased monokine production in a similar manner. Costimulation by recombinant human interferon gamma and IgE-dependent triggering had a synergistic effect on TNF production, but it had only an additive action on IL-6 synthesis (respective increase index: 9.8 compared with 2.9 and 9.8 compared with 2.1, respectively, for BM from control and asthmatic subjects).(ABSTRACT TRUNCATED AT 250 WORDS)     

Staphylococcal protein A primed leukocytes enhance the autologous mixed lymphocyte reaction

Human peripheral blood mononuclear cells (PBMC) were preincubated for 3 days in medium alone or with various mitogens then washed and irradiated. The preincubated cells then were cultured with autologous T-cells in an autologous mixed lymphocyte reaction (AMLR). Staphylococcal protein A (SPA) pretreatment of PBMC enhanced autologous T-lymphocyte proliferation from 1375 +/- 321 cpm (mean +/- SEM untreated PBMC) to 42,467 +/- 7,985 cpm (SPA primed PBMC) (p less than 0.01). The ability of SPA treated PBMC to enhance the AMLR was not simply a reflection of their proliferation in preculture, as PBMC precultured with phytohemagglutinin and concanavalin A showed greater proliferation than SPA-treated PBMC yet only minimally enhanced the AMLR. Kinetic studies and pre-exposure of PBMC to graded doses of gamma radiation showed that SPA augmentation of the AMLR was mediated by 2 components which differed in kinetics and radiosensitivity. Although incubation of PBMC with SPA did not increase the percentage of cells with detectable surface Ia antigen, SPA did increase the density of Ia in the preincubated cells. Cell separation studies revealed that SPA enhancement of the AMLR was not mediated by T-cells, but was mediated by a non-adherent non-E-rosetting fraction of cells. SPA enhancement of the AMLR was associated with an increased Ia density in the stimulator population but not with an increase in Ia positive cells and was mediated by proliferation-dependent and proliferation-independent mechanisms.     

Bronchial responsiveness is not increased by bronchoalveolar and bronchial lavage performed after allergen challenge

Nonspecific bronchial responsiveness was studied in 23 allergic patients with a history of rhinitis and/or bronchial asthma who underwent fiberoptic bronchoscopy with bronchoalveolar and bronchial lavage (BAL-BL) 4h (Group A) or 24 h (Group B) after an allergen inhalation challenge. In all patients, the dose of methacholine causing an FEV1 fall of 15% (PD15) was determined at baseline, 24 h before allergen challenge. Methacholine bronchial challenge was repeated 1 h before BAL-BL in patients of both groups and again 12 to 14 h after BAL-BL in Group A and 24 h after BAL-BL in Group B. In patients of Group A, the values of methacholine PD15 after BAL-BL were not significantly different from those determined before BAL-BL. This was also the case in patients in whom bronchial responsiveness was increased after allergen challenge. In patients of Group B, methacholine PD15 was significantly decreased after allergen challenge, and this decrease was correlated with the occurrence and the severity of the late asthmatic reaction. Even in patients who showed dual asthmatic reactions and an increased responsiveness after allergen challenge, methacholine PD15 was not further decreased after BAL-BL. These data support the safety of a procedure combining bronchial allergen challenge with BAL-BL, which can be used for studies on the pathophysiology of bronchial asthma.     

Adaptive immune responses of patients with asthma to the attachment (G) glycoprotein of respiratory synctial virus.

A history of acute bronchiolitis in infancy caused by respiratory syncytial virus is a risk factor for recurrent wheezing in early childhood. Because the attachment (G) protein sensitizes mice for pulmonary eosinophilia and because Th2 cells are central in the pathogenesis of asthma, plasma and peripheral blood mononuclear cells (PBMC) from donors with asthma and from healthy donors were evaluated for anti-G protein responses. A significant trend connecting severity of asthma with anti-G protein IgG1 and IgG2 titers was observed. The correlation between anti-F protein IgG3 titers and asthma severity approached significance. Peptide mapping studies revealed that more positive recall responses (interferon-gamma and interleukin-10 secretion) occurred after PBMC from donors with asthma were stimulated with peptides representing the nonglycosylated domain of G protein. The same peptides elicited more positive recall responses (proliferation and interferon-gamma secretion) in the PBMC of healthy donors. These data suggest that a mechanism may exist whereby adaptive immune responses against G protein contribute to wheezing.     

对慢性喘息型支气管炎气道反应性特点及其本质的探讨

目的 研究慢性喘息型支气管炎对乙酰甲胆碱和运动激发试验的气道反应性特点,并对其本质进行初步探讨。方法 对诊断明确的支气管哮喘患者,单纯型慢性支气管炎患者及慢性喘息型支气管炎患者分别进行乙酰甲胆碱吸入激发和运动激发试验,观察血嗜酸嗜酸粒细胞计数,血ＩｇＥ水平并测定慢性喘息型支气管炎患者血肖嗜酸细胞阳离子蛋白含量。     

Treatment with AM3 restores defective T-cell function in COPD patients

BACKGROUND: Lymphocyte alterations have been associated with an increased prevalence of acute respiratory infections in COPD patients. AM3 is an oral immunomodulator that normalizes the defective functions of peripheral blood natural killer and phagocytic cells in COPD patients and improves their health-related quality of life. OBJECTIVES: To characterize putative systemic abnormalities of the T-cell compartment in COPD patients, and to investigate whether AM3 can restore such abnormalities. DESIGN: The study was a randomized, prospective, double-blind, placebo-controlled trial in a cohort of COPD patients. The results were also compared to those of nonsmoker and ex-smoker healthy control subjects. SETTING: Outpatient departments of four hospitals. PATIENTS: Seventy COPD patients were randomized to receive either AM3 or a placebo orally for 90 consecutive days. Populations of 36 healthy nonsmokers and 36 healthy ex-smokers were used as control subjects. MEASUREMENTS: Peripheral blood mononuclear cell (PBMC) proliferation and production of interleukin (IL)-2, IL-4, IL-12p40, tumor necrosis factor-alpha, and interferon (IFN)-gamma proteins in response to the T-cell polyclonal mitogens were assessed at baseline and at the end of treatment. RESULTS: The proliferative response was significantly decreased in COPD patients. Decreased production of IFN-gamma was the only defect in the profiles of the cytokine measures, and was selectively observed in COPD patients, but not in nonsmoker and ex-smoker healthy control subjects. Treatment with AM3 significantly restored the PBMC proliferative response to polyclonal mitogens and significantly promoted stimulated IFN-gamma production in these patients. The normalization of these proliferative responses was not related to significant variations in the numbers of peripheral blood monocytes, CD3+, CD4+, CD8+ cells or of any major na?ve/memory/activated T-cell subset. The increased IFN-gamma production in the AM3 study arm was associated with an increase in the mean of number of IFN-gamma molecules produced per CD8+ T cells. CONCLUSIONS: PBMCs of COPD patients showed clear functional T-lymphocyte abnormalities that are rescued by AM3 treatment.     

Cellular events in the bronchi in mild asthma and after bronchial provocation

We have undertaken detailed cellular and ultrastructural examination of bronchial biopsies and bronchial lavage fluid from allergic asthmatic patients in order to determine the nature and degree of the inflammatory processes in mild allergic asthma. Eight atopic asthmatic patients (mean PC20 histamine, 0.90 mg/ml) and four nonasthmatic control subjects underwent fiberoptic bronchoscopy. All asthmatic subjects were clinically stable for 2 wk prior to bronchoscopy and required either no treatment or inhaled albuterol alone. A single 50-ml bronchial wash was undertaken, followed by endobronchial biopsy of subcarinae. These procedures were repeated in the asthmatic subjects 18 h after bronchial provocation with allergen or methacholine. Subsequently, all subjects underwent bronchial reactivity testing with inhaled histamine. The clinical and physiologic data were not revealed to the pathologist interpreting the specimens. The asthmatic subjects shed a significantly greater number of epithelial cells into the lavage fluid than did the nonasthmatic subjects (7.23 versus 1.48 x 10(4)/ml, p = 0.048). There was a statistically significant inverse correlation between the lavage epithelial cell count and bronchial reactivity (rho = -0.64, p = 0.03). In the asthmatic subjects, but not in the control subjects, there was extensive deposition of collagen beneath the epithelial basement membrane, mast cell degranulation, and mucosal infiltration by eosinophils, which exhibited morphologic evidence of activation. Eosinophils, monocytes, and platelets were found in contact with the vascular endothelium, with emigration of eosinophils and monocytes in the asthmatic subjects. These changes were found irrespective of bronchial challenge with allergen. We conclude that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.     

支气管哮喘患者痰白细胞介素16的测定及其意义

目的探讨白细胞介素１６（ＩＬ１６）在支气管哮喘发病机制中的作用。方法收集１２例过敏性哮喘患者、８例非过敏性哮喘患者、１０例过敏性体质患者和１０名正常对照者的痰液,以酶联免疫吸附测定法测定痰中ＩＬ１６的含量,并以免疫染色技术检测ＣＤ＋４细胞和活化嗜酸细胞（ＥＧ２细胞）数。结果哮喘患者无论是过敏性还是非过敏性,痰液中ＩＬ１６水平与过敏体质但无哮喘的患者和正常组比较,差异有显著性（Ｐ＜０．０１）。急性发作期哮喘患者经治疗后ＩＬ１６水平能达缓解期水平。此外,痰液中ＣＤ＋４细胞和ＩＬ１６水平比较呈显著正相关（ｒ＝０．７６,Ｐ＜０．０１）,痰液中ＥＧ２细胞数与ＩＬ１６水平呈显著正相关（ｒ＝０．６１,Ｐ＜０．０１）。结论ＩＬ１６参与了哮喘的发病过程,其机制可能是通过募集ＣＤ＋４Ｔ细胞从而在ＣＤ＋４Ｔ细胞所介导的哮喘气道嗜酸细胞炎症反应中发挥作用。     

Assay of IL-22 and IL-25 in serum,whole blood,and peripheral blood mononuclear cell cultures of patients with severe asthma

BackgroundAlthough some studies show that IL-22 and IL-25 play critical roles in the pathogenesis of asthma, little is known about the systemic production of these cytokines. The aim of this study was to assay IL-22 and IL-25 in serum, in mitogen-activated whole blood (WB), and in mitogen-activated peripheral blood mononuclear cell (PBMC) cultures of patients with severe asthma.MethodsIn this cross-sectional study, a questionnaire was prepared to determine the severity of asthma. Through the questionnaire, information including clinical signs, clinical symptoms, and past medical history were acquired. Information collected allowed all patients who were active or ex-smokers to be excluded. A trained observer assessed airway reversibility, peak flowmetry, and spirometry in the remaining patients. Twenty-one patients and simultaneously, twenty age- and sex-matched healthy controls were selected. Sterile blood (10 ml) was taken from each study participant. Sera were isolated and anticoagulant blood used for WB and PBMC cultures and haematological tests. Phytohaemagglutinin and lipopolysaccharide (LPS) were used to activate WB and PBMC. The data from these two groups were compared using Student's t-test.ResultsAlthough the total white blood cell count was elevated in the asthmatic group, other haematological indices, including IL-22 and IL-25 levels in the asthmatic group were not significantly (p > 0.05) different from controls.ConclusionsThe levels of IL-22 and IL-25 in patients with severe asthma are no higher than those of non-asthmatic individuals. Any major role for IL-22 and IL-25 in severe asthma is likely to be localised to the lungs and bronchial tissues.