interleukin-8 and Hypersensitivity

The incidences of childhood allergies have been increasing in recent years in many parts of the world. The development of allergic disorders is attributed to a complex series of interactions between individuals' genetic backgrounds and their immune and psychoneurotic responses to environmental factors. Among the various possible environmental causes of childhood allergies, the early exposure of developing infants to air pollutants and the presence of persistent chemical pollutants such as pesticides have been suggested most frequently. Therefore, it is very important to obtain epidemiological evidence of direct associations between clearly defined adverse health effects and exposure to low levels of pollutants. However, there are no useful biomarkers for assessing such associations. Thus, we planned to establish reliable health-related biomarkers that could be used to investigate these relationships in children. The serum concentrations of several sub-types of polychlorinated biphenyl (PCB) congeners were found to be significantly correlated with interleukin (IL)-8 mRNA expression among asthmatic children. In addition, IL-22 mRNA expression was found to be particularly useful for detecting the effects of environmental pollutants, especially PCB congeners, in a sub-population of vulnerable children who exhibited positive immunoglobulin E (IgE) responses to milk or egg. Furthermore, we detected significant differences in IL-22 mRNA expression between the IgE-negative non-asthmatic subjects and the asthmatic children who exhibited positive IgE reactions toward egg or milk. In conclusion, IL-8 and IL-22 mRNA expressions could be useful biomarkers for detecting sub-populations of children who are particularly vulnerable to the adverse health effects of environmental pollutants, especially PCBs.

Topics: Animals; Asthma; Biomarkers; Child, Preschool; Environmental Exposure; Humans; Hypersensitivity; Immunoglobulin E; Infant; Interleukin-22; Interleukin-8; Interleukins; Japan; Milk; Molecular Epidemiology; Polychlorinated Biphenyls; Real-Time Polymerase Chain Reaction; RNA, Messenger

The local inflammatory response that occurs after repeated exposure to allergens or during the late-phase reaction results from a complex network of interactions between inflammatory cells (mast cells, eosinophils, macrophages) and resident cells belonging to the lung structure itself like EC, fibroblasts, or bronchial epithelial cells. Among structural cells, EC represent critical elements: they control leukocyte traffic through the expression of adhesion molecules; they are also able to amplify leukocyte activation through the production of proinflammatory cytokines like IL-1, IL-6, or of chemokines like IL-8. Three cell models have been successively considered. When supernatants of alveolar macrophages, recovered from patients exhibiting a late asthmatic response after allergen exposure, were tested on HUVEC cultures, a TNF alpha-dependent ICAM-1 and E-selectin overexpression was observed. Among mast-cell mediators, histamine was already known to induce a rapid and transient expression of P-selectin; we demonstrated that histamine also induced an IL-6 and IL-8 secretion by HUVEC, which was concentration-dependent and inhibited by H1 or H2 receptor antagonists. Finally purified eosinophils obtained from donors with hypereosinophilia similarly increased adhesion molecule expression and chemokine production. The precise nature of the eosinophil product(s) involved in this process is currently under investigation.

Topics: Asthma; Bronchi; Cell Adhesion Molecules; Cell Communication; Endothelium, Vascular; Eosinophils; Humans; Hypersensitivity; Interleukin-8; Macrophages, Alveolar; Mast Cells; Microcirculation; Models, Biological; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factor-alpha

Topics: Aminopeptidases; Animals; Capillary Permeability; Chemotactic Factors; Chemotactic Factors, Eosinophil; Chemotaxis, Leukocyte; Complement C5; Eosinophilia; Guinea Pigs; Hypersensitivity; Immunoglobulin G; Inflammation; Interleukin-8; Lymphokines; Macrophages; Monocytes; Neutrophils; Rabbits; Rats; Sialoglycoproteins

The events which lead to airway narrowing in bronchial asthma are complex. There is little doubt that mast cell-derived pharmacological agents are involved, at least in part, in the initiation of the asthmatic response. However, the inflammatory response which follows mast cell activation might have more relevance to the daily pattern of asthma than the direct effects of mediators on bronchial tissue. Although the IgE mediated release of mediators from sensitized mast cells seems to play a role in pathogenesis in some individuals for some of the time, there is now increasing awareness that mast cells are also triggered by a number of non-immunological stimuli such as exercise/cold air, infection and agents which activate the complement system. Mast cell mediators are either pre-formed within granules or generated from membrane-bound phospholipids. The pre-formed mediators include histamine, various chemotactic peptides including ECF-A and the high molecular weight neutrophil chemotactic factor (NCF), proteases, glycosidases, and the heparin proteoglycan. The membrane-derived agents include the lipoxygenase products (e.g. LTB4 and the "SRS-A" leukotrienes-LTC4/D4/E4), prostaglandins and thromboxane in addition to the PAF-ace-tether (AGEPC). The mediators are diverse both in chemical composition and modes of actions. However, many of the pathological features of bronchial asthma can be explained on the basis of their recognised actions. These can be summarised as follows. Bronchial smooth muscle constriction (histamine, LTC4, LTD4, LTE4, PGF2 alfa, PGD2 and PAF); mucosal oedema (increased permeability--histamine, LTC4, LTD4 and PAF; vasodilation--PGD2, PGE2); mucous plugging (histamine, mono-HETEs and LTC4); inflammatory cell infiltrate (NCF, ECF-A peptides, HETEs, LTB4 and PAF); desquamation of epithelium (proteases, glycosidases, together with lysosomal enzymes, and basic proteins derived from neutrophils and eosinophils). It is likely that mild, easily reversible, episodic asthma is due largely to bronchial smooth muscle contraction whereas the late sustained response is more indicative of an inflammatory response, and dependent on the infiltration of neutrophils and eosinophils as the result of mediators which recruit and activate leucocytes. Much of the evidence for this is based on the demonstration that NCF concentrations in the serum are elevated during early and late phase, antigen- and exercise-induced asthma. Moderate to severe asthma is likely t

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Asthma; Asthma, Exercise-Induced; Bronchitis; Chemotactic Factors; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-8; Mast Cells; Platelet Activating Factor; SRS-A

Allergy against implant materials is discussed controversially and still not fully understood. Despite these controversies, a relevant number of patients receive hypoallergenic knee implants. The aim of this study was to compare a new coating system with the standard implant in total knee arthroplasty (TKA). Additionally, the influence of proinflammatory cytokines on patient-reported outcome measures (PROMs) was investigated.. 120 patients without known metal allergy and without previous metal implants were included. The patients were randomized to receive a coated or standard TKA of the same knee system. 105 patients completed the 5 year follow-up. Patient-reported outcome measures (PROMs) including knee function (Oxford Knee Score, OKS), quality of life (SF36) and UCLA activity scale were assessed. Additionally, several cytokines with a possible role in implant allergy were measured in patient`s serum (IL-1beta, IL-5, IL-6, IL-8, IL-10, IP-10, IFN γ, TNF α). Group comparison was performed using Mann-Whitney U test for continuous values and chi-square test for categorical values.. There were no differences in PROMs between both groups at any follow-up. The majority of patients demonstrated no elevation of the measured blood cytokines. The blood cytokine pattern after 5 years demonstrated no differences between study groups. There was a significant association between elevated IL-8 values and worse results in the overall OKS (p = 0.041), the OKS function component (p = 0.004), the UCLA activity scale (p = 0.007) and the physical component of SF36 (p = 0.001).. There were no problems with the new coating during mid-term follow-up and no differences in PROMs between coated and standard TKA. Patients with an increased inflammatory response demonstrated worse functional results, regardless of the implant.. I.. The study protocol was registered in the US National Institutes of Health's database ( http://www.. gov ) registry under NCT00862511.

Topics: Arthroplasty, Replacement, Knee; Cytokines; Humans; Hypersensitivity; Interleukin-8; Knee Joint; Knee Prosthesis; Osteoarthritis, Knee; Patient Reported Outcome Measures; Quality of Life; Treatment Outcome

Women in poor urban neighborhoods have high rates of stress and allergic diseases, but whether stress or stress correlates such as depression promote inflammatory and type 2 cytokine responses is unknown.. To examine associations among external stressors, perceived stress, depression, and peripheral blood mononuclear cell cytokine responses of mothers enrolled in the Urban Environment and Childhood Asthma Study and test the hypothesis that stress would be positively associated with type 2 and selected proinflammatory (tumor necrosis factor-α and interleukin-8) responses.. Questionnaire data from mothers living in 4 inner cities included information about external stress, stress perception, and depression. The external stress domains (interpersonal problems, housing, and neighborhood stress) were combined into a Composite Stressor score. Peripheral blood mononuclear cells were stimulated ex vivo and cytokine responses to innate, adaptive, and polyclonal immune stimuli were compared with stress and depression scores for 469 of the 606 study participants.. There were no significant positive associations between Composite Stressor scores, perceived stress, or depression scores and proinflammatory or type 2 cytokine responses, and these findings were not modified by allergy or asthma status. There were some modest associations with individual stressors and cytokine responses, but no consistent relations were noted. Depression was associated with decreased responses to some stimuli, particularly dust mite.. Composite measurements of stressors, perceived stress, or depression were not positively related to proinflammatory or type 2 cytokine responses in these young urban women. These data do not support the hypothesis that these factors promote cytokine responses associated with allergy.. ClinicalTrials.gov, identifier NCT00114881.

Topics: Adolescent; Adult; Asthma; Cytokines; Depression; Female; Humans; Hypersensitivity; Interleukin-8; Leukocytes, Mononuclear; Mothers; Residence Characteristics; Stress, Psychological; Tumor Necrosis Factor-alpha; Urban Population; Young Adult

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. Recently, we showed that allergic mothers had higher concentrations of IL-4 and lower concentrations of ovalbumin-specific IgA in their breast milk than nonallergic mothers. The aim of this study was to investigate the concentrations of chemokines and cytokines that are chemotactic to cells involved in allergic reactions in breast milk from allergic and nonallergic mothers. Cytokine and chemokine concentrations were determined with ELISA in colostrum and mature milk samples from 23 mothers with and 25 mothers without atopic symptoms. IL-8 was detected in all milk samples. RANTES (regulated on activation, normal T cell expressed and secreted), eotaxin, and IL-16 were detected in 50%, 76%, and 48%, respectively, in colostrum and less commonly in mature milk. Macrophage inflammatory protein-1alpha, however, could not be detected in any of the samples. The concentrations of IL-8 and RANTES were higher in breast milk from allergic, compared with nonallergic, mothers. In conclusion, the presence of chemoattractant factors in breast milk may be responsible for the traffic of leukocytes from the maternal circulation to the breast milk. The higher concentrations of RANTES and IL-8 in allergic mothers may partly explain the controversy regarding the protective effect of breast-feeding against the development of allergy by stronger chemotaxis and activation of cells involved in allergic diseases, and possibly by elevated IgE production.

Topics: Chemokine CCL11; Chemokine CCL4; Chemokine CCL5; Chemokines; Chemokines, CC; Colostrum; Cytokines; Female; Humans; Hypersensitivity; Immunity, Maternally-Acquired; Interleukin-16; Interleukin-8; Macrophage Inflammatory Proteins; Milk, Human; Prospective Studies

We have demonstrated the detection of proallergic cytokines in the nasal secretions after antigen challenges. Our aim was to determine the secretion kinetics of chemokines (interleukin [IL]-8, macrophage inflammatory protein-1 alpha [MIP-1 alpha], and RANTES) and other cytokines (IL-1 beta and granulocyte/macrophage colony-stimulating factor [GM-CSF] after allergen challenges and their inhibition by steroid therapy. Ten allergic patients were given either beclomethasone dipropionate (BDP) or placebo in a double-blind, randomized, crossover manner. Allergen challenges were performed after 1 wk of treatment. Nasal secretions were collected serially for 11 h after allergen challenge by a matrix method. Subjects maintained symptom scores at each time point of nasal secretion recovery. Cytokines were measured by specific enzyme-linked immunosorbent assays. The mean peak values for each cytokine and total symptom scores during the early (ER) and/or late-phase reactions (LPR) were significantly reduced during the BDP treatment period (p < 0.05). The levels of cytokine correlated (p < 0.05) with corresponding total symptom scores during ER (IL-1 beta and MIP-1 alpha) and LPR (all cytokines). Our findings document local elevations of IL-1 beta, GM-CSF, and chemokines in the nasal secretions after allergen challenges and their inhibition by steroids. We speculate that the inhibition of cytokine production and secretion in the nasal mucosa may contribute to the clinical efficacy of topical steroids.

Topics: Beclomethasone; Chemokine CCL4; Chemokine CCL5; Cross-Over Studies; Cytokines; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypersensitivity; Interleukin-1; Interleukin-8; Kinetics; Lymphokines; Macrophage Inflammatory Proteins; Monokines; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests

Secretion of translationally controlled tumor protein (TCTP) was found in body fluids during the late phase of allergic reactions, implicating TCTP in allergic diseases. Furthermore, blocking TCTP has been shown to be helpful in treating asthma and allergies in animal models. The objectives of this study were to produce anti-TCTP monoclonal antibodies (mAbs), test their ability to inhibit the cytokine-like function of dimeric TCTP (dTCTP) in vitro and to assess their therapeutic effects in a murine model of ovalbumin (OVA)-induced airway inflammation. We first verified the inhibitory effects of 4 anti-TCTP mAbs on dTCTP-induced secretion of IL-8 in BEAS-2B cells. To investigate the anti-inflammatory effect of anti-TCTP mAbs on allergic airway inflammation, we treated OVA-sensitized mice with anti-TCTP mAbs before OVA challenge. The changes in bronchoalveolar lavage fluid (BALF) cells, IL-4, IL-5, and IL-13 levels in both BALF and lung homogenates, plasma levels of OVA-specific IgE, and lung tissues were analyzed. We found that JEW-M449 anti-TCTP mAb bound to the flexible loop of TCTP and significantly inhibited dTCTP-induced IL-8 release, making it the most effective inhibitor in our study. We also found that treatment with JEW-M449 significantly reduced the infiltration of inflammatory cells and suppressed the OVA-induced upregulation of type 2 cytokines in both BALF and lung homogenates in a dose-dependent manner. In addition, JEW-M449 significantly attenuated the degree of goblet cell hyperplasia and mucus secretion. Our results demonstrate that specific targeting of the flexible loop of TCTP is a potent strategy for treating airway inflammatory diseases.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Hypersensitivity; Inflammation; Interleukin-8; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Tumor Protein, Translationally-Controlled 1

Topics: Asthma; Cell Differentiation; Cell Line; Cells, Cultured; Cytokines; Gene Expression Profiling; Humans; Hypersensitivity; Intercellular Adhesion Molecule-1; Interleukin-8; Lipopolysaccharides; Mucin 5AC; Proto-Oncogene Proteins c-ets; Respiratory Hypersensitivity; Respiratory Mucosa; RNA, Antisense; RNA, Long Noncoding; Up-Regulation

Asthma is a heterogeneous disease characterized by multiples respiratory symptoms; this is a polygenic entity that involves a complex interaction of environmental factors and inherent to the individual. To understand the development of asthma, some phenotypes have been proposed.. This work's purpose was to explore different molecules related to asthma development and to define each phenotype's specific characteristics.. 96 adult patients diagnosed with asthma before any treatment were enrolled in the protocol. Spirometric parameters, circulating leukocytes, serum IgE, body mass index, exhaled nitric oxide (FENO), and leukotrienes (LTB4) in urine were determined in each patient. The presence of asthma phenotypes proposed by the Global Initiative for Asthma (GINA) were explored: A) Allergic asthma, B) Non-allergic asthma, C) Late-onset asthma, D) Asthma with persistent airflow limitation, and E) Asthma with overweight and obesity.. In the cohort analyzed, we found four of phenotypes proposed by GINA; however, these phenotypes overlapped, due to this, 4 groups were integrated with allergic, non-allergic and obese patients, which were the main phenotypes. The main overlap was that of patients not-obese allergic, and was characterized by earlier onset, elevated levels of IgE, LTB4 and inflammasome related cytokines. Non-allergic patients had a significant association between interleukin (IL)-18 and IL-18 binding protein (BP) with narrow ratio between these cytokines. Finally, LTB4 had remarkable capacity to discriminate between allergic and not allergic patients.. Asthmatic phenotypes exist as interrelated characteristics and not as discrete entities. High levels of leukotrienes and IgE are hallmarks in the allergic phenotype of asthma.

Topics: Adult; Age of Onset; Asthma; Biomarkers; Cytokines; Eosinophils; Female; Humans; Hypersensitivity; Immunoglobulin E; Inflammasomes; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Interleukin-18; Interleukin-8; Leukotrienes; Male; Middle Aged; Overweight; Phenotype; Transforming Growth Factor beta

Allergic diseases are a major health concern worldwide. Pollens are important triggers for allergic rhinitis, conjunctivitis and asthma. Proteases released upon pollen grain hydration appear to play a major role in the typical immunological and inflammatory responses that occur in patients with allergic disorders. In this study, we aimed to identify specific proteolytic activity in a set of pollens with diverse allergenic potential. Diffusates from

Topics: Cell Line; Chenopodium; Eucalyptus; Humans; Hypersensitivity; Interleukin-6; Interleukin-8; Peptide Hydrolases; Plantago; Pollen; Receptor, PAR-2; Water

Asthma is a complex disease comprising various phenotypes and endotypes, all of which still need solid biomarkers for accurate classification. In a previous study, we defined specific genes related to asthma and respiratory allergy by studying the expression of 94 genes in a population composed of 4 groups of subjects: healthy control, nonallergic asthmatic, asthmatic allergic, and nonasthmatic allergic patients. An analysis of differential gene expression between controls and patients revealed a set of statistically relevant genes mainly associated with disease severity, i.e.,

Topics: Adult; Aged; Asthma; Biomarkers; Chitinase-3-Like Protein 1; Diagnosis, Differential; Disease Progression; Female; Humans; Hypersensitivity; Interleukin-10; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Phenotype; Sensitivity and Specificity

Allergic diseases can expand at any age as a result of complicated interaction of environmental and genetic factors. Through the years, studies have found that allergic diseases are primarily described by elevated Th2 pathway activation, leading to increased serum IgE levels, allergen reactivity, blood eosinophil counts and secreted interleukins.. A total of 20 patients with allergy and 20 matched controls participants were recruited for the study. A study was designed with the framework of an ongoing project at the Regional Children's Hospital in Olsztyn on the analysis of the immune profile of children with allergy and asthma. Diagnosis was conducted by medical specialists. Whole blood samples were collected and serum IL's and chemokin levels were made using ELISA kits.. Results demonstrated that in comparison to the controls, the individuals with allergy showed significantly higher concentration of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13 and TNF-α. We also demonstrated significant correlations between the levels of cytokines which implies the presence of an interactive network between them. The results of ROC analysis indicated the 3-factors (IL-1β, IL-4, IL-8) could be additional, helpful biomarkers in better diagnosis of allergy.. In this study, serum levels of cytokine differed among children with allergy. However, the findings of this support the possibility of using an appropriate selection of serum cytokine for the diagnosis allergy and emphasize the need to standardize quantitative methods for serum analysis.

Topics: Biomarkers; Child; Child, Preschool; Female; Humans; Hypersensitivity; Inflammation; Interleukin-1beta; Interleukin-4; Interleukin-8; Male; Reference Standards; Skin Tests; Th2 Cells

The effects of asiaticoside (AS) on allergic responses mediated by mast cells were investigated. AS showed no obvious cytotoxicity on RPMCs (rat peritoneal mast cells). AS reduced the intracellular calcium in RPMCs and deprived the histamine release and degranulation. AS also decreased the generation of antigen-induced tumor necrosis factor α, interleukin (IL)-4, IL-8, and IL-1β in RBL-2H3 cells sensitized by IgE. The suppression of AS on pro-inflammatory cytokines was related with the activation of the intracellular FcεRI and the inhibition of the nuclear factor-κB signaling pathway. In addition, AS disabled the phosphorylation of antigen-induced Syk, Lyn, Gab2, and PLCγ1, thus suppressing the downstream Akt phosphorylation and MAPKs pathways. It also increased HO-1 and Nrf2 expression time dependently. In summary, we demonstrate that AS suppresses the allergic inflammation mediated by mast cells and this effect might be mediated by FcεRI-dependent signaling pathways.

Topics: Animals; Cell Degranulation; Cells, Cultured; Histamine Release; Hypersensitivity; Immunoglobulin E; Interleukin-8; Male; Mast Cells; Mice; Mice, Inbred BALB C; NF-kappa B; Phosphorylation; Rats; Rats, Sprague-Dawley; Signal Transduction; Triterpenes

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Activating Transcription Factor 3; Allergens; Animal Testing Alternatives; Biological Assay; Cell Survival; Cells, Cultured; Dinitrochlorobenzene; Glutamate-Cysteine Ligase; Haptens; HSP40 Heat-Shock Proteins; Humans; Hypersensitivity; Interleukin-8; Keratinocytes; L-Lactate Dehydrogenase; Local Lymph Node Assay; NF-E2-Related Factor 2; Purinergic P2X Receptor Antagonists; RNA, Small Interfering

Although protection against infectious diseases has been observed among breastfed infants as compared to formula-fed infants, possible benefits of breastfeeding by allergic mothers for allergy prevention remain controversial.. The aims of this study were to determine whether maternal allergy would influence immune markers (secretory immunoglobulin A [sIgA], interleukin-8 [IL-8], soluble CD14 [sCD14]) in colostrum and the associations between maternal allergy and fecal sIgA levels in breastfed infants.. Study subjects were enrolled from the Prediction of Allergies in Taiwanese Children (PATCH) birth cohort study. Colostrum samples were obtained from 98 lactating mothers. Stool samples were collected from 108 infants within 5 days after birth and at 2 and 4 months of age. We compared concentrations of sIgA, IL-8, and sCD14 in colostrum between mothers with and without a history of allergic disease and allergic sensitization. We also compared fecal sIgA levels between breastfed and formula-fed infants and between infants with allergic and nonallergic mothers.. The sIgA concentrations were significantly higher in colostrum from allergic mothers than from nonallergic mothers (P = .01) and from allergic mothers who were immunoglobulin E (IgE) sensitized compared to nonallergic mothers who were not IgE sensitized (P = .023). Breastfed infants had significantly higher fecal sIgA levels as compared to formula-fed infants, regardless of whether their lactating mothers had an allergy (P < .05).. We found that breastfeeding is associated with increased infants' fecal sIgA levels and may have potential protective effects to the infants during the first 4 months of life, regardless of whether their lactating mothers have allergies.

Topics: Adult; Biomarkers; Breast Feeding; Case-Control Studies; Colostrum; Feces; Female; Follow-Up Studies; Humans; Hypersensitivity; Immunoglobulin A, Secretory; Infant; Infant Formula; Infant, Newborn; Interleukin-8; Lipopolysaccharide Receptors; Male; Prospective Studies; Protective Factors

Recent studies have shown that fine particulate matter (PM2.5) is associated with multiple adverse health outcomes and PM2.5-induced oxidative stress is now commonly known as a proposed mechanism of PM2.5-mediated toxicity. However, the association between allergic symptoms in children and exposure to PM2.5 has not been fully elucidated, particularly the role of PM2.5 on the indoor environment involved in allergy or non-allergy is unknown. The aim of the present study was to explore whether indoor PM2.5 from the homes of children with allergic symptoms had more increased risks of allergy than that of healthy ones and then compare the toxicity and inflammatory response of them. In this study, indoor PM2.5 was collected from the homes of schoolchildren with allergic symptoms and those of healthy ones respectively, and components of PM2.5 were analyzed. PM2.5-mediated oxidative damage and inflammatory response were further evaluated in mouse peritoneal macrophages based on its effects on the levels of reactive oxygen species accumulation, lipid peroxidation, DNA damage or cytokine production. It seems that oxidative stress may contribute to PM2.5-induced toxicity, and PM2.5 from the allergic indoor environment produced more serious toxic effects and an inflammatory response on mouse peritoneal macrophages than that from a non-allergic indoor environment.

Topics: Air Pollutants; Air Pollution, Indoor; Animals; Cells, Cultured; Child; China; DNA Damage; Female; Glutathione; Humans; Hypersensitivity; Interleukin-8; Lipid Peroxidation; Macrophages, Peritoneal; Male; Mice; Oxidative Stress; Particulate Matter; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood.. To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects.. 18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points.. Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells.. Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.. NCT01792232.

Topics: Adult; Allergens; Biomarkers; Bronchoalveolar Lavage; Bronchoscopy; Chemokine CCL2; Eosinophil Cationic Protein; Eosinophils; Female; Gasoline; Genotype; Glutathione Transferase; Humans; Hypersensitivity; Immunoglobulin E; Inflammation; Inhalation Exposure; Interleukin-5; Interleukin-8; Male; Middle Aged; Neutrophils; Respiratory Hypersensitivity; Vehicle Emissions

Human blood basophils have recently gained interest in addition to their function as allergic effector cells. Previous work suggests the involvement of innate immune mechanisms in the development and exacerbation of allergic responses, which might be mediated by basophils. We assayed the expression levels of Toll-like receptor (TLR) 1, 2, 4 and 6 on purified basophils from birch pollen-, house dust mite-, and non-allergic individuals. Additionally, we compared cytokine and chemokine secretion upon TLR stimulation in these basophil donor groups. Expression of TLR4 on the basophils of the allergic donor groups was decreased and CXCL8 secretion was elevated upon stimulation of TLR1/2 and TLR2/6 compared to the non-allergic donors. Decreased TLR expression and elevated CXCL8 secretion may represent possible mechanisms for aggravation of allergic symptoms in case of parasitic infection.

Topics: Adolescent; Adult; Basophils; Child; Female; Humans; Hypersensitivity; Interleukin-8; Male; Middle Aged; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 6; Toll-Like Receptors; Young Adult

The aim of this study is to evaluate inflammatory markers and pro-inflammatory CD14 and Toll-like Receptor 4 (TLR4) polymorphisms in workers exposed to flour dust.. Polymorphisms in TLR4 and CD14 were identified in our study population of 167 workers that included 63 healthy subjects (HS), 45 atopic subjects (A), and 59 subjects diagnosed clinically with occupational asthma/rhinitis (OAR). Endpoint measures in this study included fractional exhaled nitric oxide and serum concentrations of interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α).. We identified a polymorphism in CD14 (rs2569190) that may be differentially expressed (P = 0.06). IL-6 concentrations in the serum were significantly higher in the A and OAR groups (P < 0.01) than in subjects in the HS group, while IL-8 concentrations were significantly elevated only in the OAR group (P < 0.01). Interestingly, TNF-α concentrations in the OAR group were significantly reduced when compared with subjects in the HS group (P < 0.01).. Cytokines are likely a defensive response in atopic and healthy workers. A protective genotype is hypothesized for occupational asthma.

Topics: Adult; Asthma, Occupational; Case-Control Studies; Dust; Female; Flour; Humans; Hypersensitivity; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Male; Middle Aged; Polymorphism, Genetic; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

COPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, β2-adrenoceptor agonists and/or corticosteroids, do not specifically target oxidative stress, nor do they reduce chronic pulmonary inflammation and disease progression in all patients. Here, we explore the effects of Sul-121, a novel compound with anti-oxidative capacity, on hyperresponsiveness (AHR) and inflammation in experimental models of COPD. Using a guinea pig model of lipopolysaccharide (LPS)-induced neutrophilia, we demonstrated that Sul-121 inhalation dose-dependently prevented LPS-induced airway neutrophilia (up to ~60%) and AHR (up to ~90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S, and LPS-induced attenuation of blood H2S (~60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by ~80%. In immortalized human airway smooth muscle (ASM) cells, Sul-121 dose-dependently prevented cigarette smoke extract-induced IL-8 release parallel with inhibition of nuclear translocation of the NF-κB subunit, p65 (each ~90%). Sul-121 also diminished cellular reactive oxygen species production in ASM cells, and inhibited nuclear translocation of the anti-oxidative response regulator, Nrf2. Our data show that Sul-121 effectively inhibits airway inflammation and AHR in experimental COPD models, prospectively through inhibition of oxidative stress.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cell Line, Transformed; Chromans; Complex Mixtures; Disease Models, Animal; Gene Expression Regulation; Guinea Pigs; Humans; Hydrogen Sulfide; Hypersensitivity; Inflammation; Interleukin-8; Lipopolysaccharides; Lung; Male; Malondialdehyde; Myocytes, Smooth Muscle; Neutrophils; NF-E2-Related Factor 2; Oxidative Stress; Piperazines; Pulmonary Disease, Chronic Obstructive; Reactive Oxygen Species; Tars; Transcription Factor RelA

Dysregulation of neutrophil apoptosis causes pathogenesis and aggravation of allergy. S100A9 exists as one of the proteins in the neutrophils, triggering inflammatory responses by activating the immune cells. In this study, we investigated whether S100A9 affects constitutive neutrophil apoptosis by activating the monocytes in normal and allergic subjects. Supernatant from human monocytic THP-1 cells after treatment with S100A9 suppressed normal neutrophil apoptosis by inhibiting the activations of caspase 9 and caspase 3. S100A9 upregulated the release of MCP-1, IL-6, and IL-8 in THP-1 cells. An increase in cytokine was suppressed by CLI-095, a Toll-like receptor (TLR) 4 inhibitor, PP2, a Src inhibitor, rottlerin, a PKCδ inhibitor, MAP kinase inhibitors, including PD98059, SB202190, and SP600125, and BAY-11-7085, an NF-κB inhibitor. Src, PKCδ, ERK1/2, p38 MAPK, and JNK were phosphorylated by S100A9. The phosphorylation of Src and PKCδ was suppressed by CLI-095, and the activation of ERK1/2, p38 MAPK, and JNK was inhibited by CLI-095, PP2, and rottlerin. S100A9 induced NF-κB activity, and the activation was suppressed by CLI-095, PP2, rottlerin, and MAPK kinase inhibitors. In normal and allergic subjects, supernatant from normal and allergic monocytes after stimulation with S100A9 suppressed normal and allergic neutrophil apoptosis, respectively; MCP-1, IL-6, and IL-8 in the supernatant was increased by S100A9. The cytokine secretion induced by S100A9 is related to TLR4, Src, PKCδ, ERK1/2, p38 MAPK, JNK, and NF-κB. Taken together, S100A9 induces anti-apoptotic effect on normal and allergic neutrophils by increasing cytokine secretion of monocytes. These findings may help us to better understand neutrophil apoptosis regulated by S100A9 and pathogenesis of allergic diseases.

Topics: Acetophenones; Apoptosis; Benzopyrans; Calgranulin B; Caspase 3; Caspase 9; Caspase Inhibitors; Cell Line; Chemokine CCL2; Culture Media; Cytokines; Humans; Hypersensitivity; Interleukin-6; Interleukin-8; Mitogen-Activated Protein Kinase Kinases; Monocytes; Neutrophils; NF-kappa B; Pyrimidines; Signal Transduction; Sulfonamides; Toll-Like Receptor 4

Little data exist on short- and long-term effects of occupational exposure on airway and systemic inflammation in professional firefighters. We aimed to characterize airway and systemic inflammation in training firefighters with a maximum occupational exposure of 1 year compared to the long-term exposure of professional firefighters.. A questionnaire for symptoms and exposure, pulmonary function, atopy, bronchial hyper-responsiveness, and markers of inflammation in induced sputum, serum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies were assessed in a total of 92 firefighters (63 full-time professionals and 29 trainees).. Professional firefighters showed allergic bronchial sensitization documented by the presence of atopy, and eosinophilia in induced sputum, BAL and bronchial biopsies. IL-8, ECP, VEGF, and TNF-α levels were statistically significantly higher in the sputum supernatants of professional firefighters compared to the trainees (p = 0.04, p = 0.02, p = 0.04, and p = 0.02, respectively). Serum IL-8 and TNF-α levels were also statistically significantly higher in the group of professional firefighters (p = 0.04, p = 0.03, respectively). Finally, there was a linear correlation between the duration of the occupation in Service and the degree of airway and systemic inflammation.. These results indicate a "dose-response" effect of chronic exposure to a polluted environment on bronchial and systemic inflammation in professional firefighters.

Topics: Adult; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Eosinophil Cationic Protein; Eosinophils; Firefighters; Humans; Hypersensitivity; Inflammation; Interleukin-8; Male; Occupational Exposure; Respiratory Function Tests; Respiratory System; Sputum; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Studies on sCD200 (OX-2), 25-hydroxyvitamin-D (25(OH)D), homocysteine (hcy), eosinophil cationic peptide (ECP), d-dimer, CXCL8 and fractional exhale nitric oxide concentrations in allergic patients in Mediterranean regions under various climatic conditions have not been performed. In this report, blood samples were taken in May and June during times of high air pollination. This study was performed to compare serum biomolecule concentrations in allergic patients and matched controls and to evaluate the characteristics of allergic disease.. The study participants (n = 129) included 25 healthy individuals (controls) and 104 allergic patients. Consecutive patients with managed allergic disease (Group II, III, IV and V) above the age of 18 years were included.. In the control group, there was a significant positive correlation between ECP level and body mass index (BMI). Positive correlations among ECP, IgE and OX-2 levels were detected in Group IV. In Group V patients, positive correlations between age and IgE and between BMI and 25(OH)D were identified. Statistical analysis revealed positive correlations among basophil, eosinophil and OX-2 levels, and a negative correlation between ECP and age in Group V.. Overall, these data suggest that hcy, 25(OH)D and OX-2 may be useful biomarkers for conventional clinical measurements.

Topics: Adult; Age Factors; Antigens, CD; Biomarkers; Body Mass Index; Eosinophil Cationic Protein; Exhalation; Female; Fibrin Fibrinogen Degradation Products; Homocysteine; Humans; Hypersensitivity; Interleukin-8; Male; Middle Aged; Nitric Oxide; Severity of Illness Index; Sex Factors; Turkey; Vitamin D

Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state.. To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could contribute to the activation of the inflammatory state.. We silenced the expression of EGR-1 or DUSP-1 in the airway epithelial cell line NCI-H292. The cell lines were stimulated in a 24-h time course with the house dust mite allergen or poly(I:C). RNA expression profiles of cytokines were established using q-PCR and protein levels were determined in supernatants with ELISA.. The shRNA-mediated gene silencing reduced expression levels of EGR-1 by 92% (p<0.0001) and of DUSP-1 by 76% (p<0.0001). Both mutant cells lines showed an increased and prolonged response to the HDM allergen. The mRNA induction of IL-6 was 4.6 fold (p=0.02) and 2.4 fold higher (p=0.01) in the EGR-1 and DUSP-1 knock-down, respectively when compared to the induced levels in the control cell line. For IL-8, the induction levels were 4.6 fold (p=0.01) and 13.0 (p=0.001) fold higher. The outcome was largely similar, yet not identical at the secreted protein levels. Furthermore, steroids were able to suppress the poly(I:C) induced cytokine levels by 70-95%.. Deregulation of EGR-1 and/or DUSP-1 in nasal epithelium could be responsible for the prolonged activated transcriptional state observed in vivo in allergic disease. This could have clinical consequences as cytokine levels after the steroid treatment in EGR-1 or DUSP-1 knock-down remained higher than in the control cell line.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Antigens, Dermatophagoides; Cell Line; Dexamethasone; Dual Specificity Phosphatase 1; Early Growth Response Protein 1; Epithelial Cells; Gene Expression Profiling; Humans; Hypersensitivity; Inflammation; Interleukin-6; Interleukin-8; Poly I-C; Pyroglyphidae; Respiratory Mucosa; RNA Interference; RNA, Messenger; RNA, Small Interfering

Binding of allergen to IgE on basophils positively affects allergic inflammation by releasing inflammatory mediators. Recently, basophils were shown to express pattern-recognition receptors, such as toll-like receptors (TLRs), for recognizing microbe-associated molecular patterns (MAMPs) that are independent of allergen-IgE binding. In this study, we investigated whether MAMP alone can induce IL-6 production in a human basophil cell line, KU812. Stimulation with flagellin in the absence of allergen-IgE association induced IL-6 expression in KU812 cells, while stimulation with lipoteichoic acid, peptidoglycan, or poly I:C did not under the same condition. Flagellin-induced IL-6 expression was also observed in human primary basophils. Flow cytometric analysis showed that KU812 cells expressed flagellin-recognizing TLR5 both on the cell surface and in the cytoplasm while TLR2 and TLR3 were observed only in the cytoplasm. We further demonstrated that although flagellin augmented the phosphorylation of mitogen-activated protein kinases including p38 kinase, ERK, and JNK, flagellin-induced IL-6 production was attenuated by inhibitors for p38 kinase and ERK, but not by JNK inhibitors. In addition, flagellin enhanced phosphorylation of signaling molecules including CREB, PKCδ, and AKT. The inhibitors for PKA and PKC also showed inhibitory effects. Interestingly, flagellin-induced IL-6 production was further enhanced by pretreatment with inhibitors for PI3K, implying that PI3K negatively affects the flagellin-induced IL-6 production. Furthermore, DNA binding activities of NF-κB, AP-1, and CREB, which play pivotal roles in the induction of IL-6 gene expression, were increased by flagellin. These results suggest that flagellin alone is sufficient to induce IL-6 gene expression via TLR5 signaling pathways in human basophils.

Topics: Allergens; Basophils; Cell Line; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; DNA-Binding Proteins; Extracellular Signal-Regulated MAP Kinases; Flagellin; Humans; Hypersensitivity; Immunoglobulin E; Inflammation; Interleukin-6; Interleukin-8; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Peptidoglycan; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Poly I-C; Protein Kinase C-delta; Proto-Oncogene Proteins c-akt; Receptors, Pattern Recognition; RNA, Messenger; Teichoic Acids; Toll-Like Receptor 2; Toll-Like Receptor 3; Toll-Like Receptor 5; Transcription Factor AP-1

Allergic asthma can cause airway structural remodeling, involving the accumulation of extracellular matrix and thickening of smooth muscle. Tumor necrosis factor (TNF) family ligand LIGHT (TNFSF14) is a cytokine that binds herpesvirus entry mediator (HVEM)/TNFRSF14 and lymphotoxin β receptor (LTβR). LIGHT induces asthmatic cytokine IL-13 and fibrogenic cytokine transforming growth factor-β release from allergic asthma-related eosinophils expressing HVEM and alveolar macrophages expressing LTβR, respectively, thereby playing crucial roles in asthmatic airway remodeling. In this study, we investigated the effects of LIGHT on the coculture of human basophils/eosinophils and bronchial epithelial BEAS-2B cells. The expression of adhesion molecules, cytokines/chemokines, and matrix metalloproteinases (MMP) was measured by flow cytometry, multiplex, assay or ELISA. Results showed that LIGHT could significantly promote intercellular adhesion, cell surface expression of intercellular adhesion molecule-1, release of airway remodeling-related IL-6, CXCL8, and MMP-9 from BEAS-2B cells upon interaction with basophils/eosinophils, probably via the intercellular interaction, cell surface receptors HVEM and LTβR on BEAS-2B cells, and extracellular signal-regulated kinase, p38 mitogen activated protein kinase, and NF-κB signaling pathways. The above results, therefore, enhance our understanding of the immunopathological roles of LIGHT in allergic asthma and shed light on the potential therapeutic targets for airway remodeling.

Topics: Asthma; Basophils; Bronchi; Cell Adhesion; Cell Line; Cell Membrane; Coculture Techniques; Eosinophils; Epithelial Cells; Humans; Hypersensitivity; Interleukin-6; Interleukin-8; Macrophages; Matrix Metalloproteinase 9; Microscopy, Fluorescence; Recombinant Proteins; Signal Transduction; Tumor Necrosis Factor Ligand Superfamily Member 14

Respiratory tract bacterial infection can amplify and sustain airway inflammation. Intracytosolic nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is one member of the nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) family, which senses the conserved structural peptidoglycan component muramyl dipeptide (MDP) in almost all bacteria. In the present study, activation of the NOD2 ligand MDP on primary human bronchial epithelial cells (HBE) co-cultured with human basophils was investigated. Cytokines, NOD2, adhesion molecules and intracellular signalling molecules were assayed by enzyme-linked immunosorbent assay or flow cytometry. The protein expression of NOD2 was confirmed in basophils/KU812 cells and HBE/human bronchial epithelial cell line (BEAS-2B) cells. MDP was found to up-regulate significantly the cell surface expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 on basophils and HBE in the co-culture system with or without basophil priming by interleukin (IL)-33 (all P < 0·05). MDP could further enhance the release of inflammatory cytokine IL-6 and chemokine CXCL8, and epithelium-derived anti-microbial peptide β-defensin 2 in the co-culture. HBE cells were the major source for the release of IL-6, CXCL8 and β-defensin2 upon stimulation by MDP in the co-culture system. The expression of ICAM-1 and VCAM-1 and release of IL-6 and CXCL8 were suppressed by various signalling molecule inhibitors, implying that the interaction between basophils and primary human bronchial epithelial cells could be regulated differentially by the mitogen-activated protein kinase pathways and nuclear transcription factors. The results therefore provide a new insight into the functional role of basophils in innate immunity, and the link between respiratory bacteria-mediated innate immunity and subsequent amplification of allergic inflammation in the airway.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Basophils; beta-Defensins; Bronchi; Cell Communication; Coculture Techniques; Epithelial Cells; Gene Expression; Humans; Hypersensitivity; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-33; Interleukin-6; Interleukin-8; Interleukins; Mitogen-Activated Protein Kinases; Nod2 Signaling Adaptor Protein; Respiratory Tract Infections; Signal Transduction; Vascular Cell Adhesion Molecule-1

Human linkage analyses have implicated the MS4A2-containing gene locus (encoding FcεRIβ) as a candidate for allergy susceptibility. We have identified a truncation of FcεRIβ (t-FcεRIβ) in humans that contains a putative calmodulin-binding domain and thus, we sought to identify the role of this variant in mast cell function. We determined that t-FcεRIβ is critical for microtubule formation and degranulation and that it may perform this function by trafficking adaptor molecules and kinases to the pericentrosomal and Golgi region in response to Ca2+ signals. Mutagenesis studies suggest that calmodulin binding to t-FcεRIβ in the presence of Ca2+ could be critical for t-FcεRIβ function. In addition, gene targeting of t-FcεRIβ attenuated microtubule formation, degranulation, and IL-8 production downstream of Ca2+ signals. Therefore, t-FcεRIβ mediates Ca2+ -dependent microtubule formation, which promotes degranulation and cytokine release. Because t-FcεRIβ has this critical function, it represents a therapeutic target for the downregulation of allergic inflammation.

Topics: Adaptor Proteins, Signal Transducing; Calcium; Calcium Signaling; Calmodulin-Binding Proteins; Cell Degranulation; Golgi Apparatus; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-8; Mast Cells; Microtubules; Prostaglandin D2; Protein Isoforms; Receptors, IgE; RNA Interference; RNA Splicing; RNA, Messenger; RNA, Small Interfering

Recently attention has been paid to the role of cytokines in clinical pathology, since they can mediate a wide variety of biological effects. For these reasons multiplex methods have been developed to simultaneously measure numerous cytokines in individual small volume specimens. The aim of the study was to assess the usefulness of flow cytometric analysis of cytokines in peripheral blood and bone marrow plasma with Cytometric Bead Array (CBA) kits.. The study involved 59 children. Tests were performed in peripheral blood and bone marrow plasma. Human Inflammatory Cytokine Kit (IL-8, -1β, -6, -10, TNF, -12p70) and Human Th₁/Th₂/Th₁₇ Cytokine Kit (IL-2, -4, -6, -10, TNF, INF-γ, -17A) (BD Bioscience) were used. Samples were analyzed on a Cytomics FC500 flow cytometer (Beckman Coulter).. In patients diagnosed for hemophagocytic lymphohistiocytosis (HLH) (n=10) and for acute lymphoblastic leukemia (ALL) (n=12) Human Inflammatory Cytokine Kit was used. In almost all samples individual cytokines were detected in a wide range of concentrations (0.47 - 653.74 pg/ml). In samples from patients suffering from allergy (n=12) and in healthy children (n=25) Human Th₁/Th₂/Th₁₇ Cytokine Kit was used. Detection of individual cytokines was much lower: concentration range 0.09-30.17 pg/ml.. Based on our analysis the CBA test is suitable for analysis of several cytokines in small volumes of samples. A simple flow cytometer can be used for this test. The CBA test is more suitable for samples with expected increased levels of cytokines. When the levels of cytokines are low, the sensitivity of the CBA test can be too low.

Topics: Biomarkers; Bone Marrow; Child; Child, Preschool; Cytokines; Female; Flow Cytometry; Humans; Hypersensitivity; Interleukin-2; Interleukin-8; Lymphohistiocytosis, Hemophagocytic; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reference Values; Retrospective Studies

The mechanisms that underlie allergic transfusion reactions (ATRs) are not well characterized, but likely involve recipient, donor, and product factors. To assess product factors associated with ATRs, we investigated candidate mediators in apheresis platelet (PLT) products associated with ATRs and controls.. Using bead-based and standard enzyme-linked immunosorbent assays, we tested supernatants from 20 consecutive apheresis PLT transfusions associated with ATRs and 30 control products for concentrations of mediators in three categories: acute inflammatory mediators, direct agonists of basophils and mast cells, and growth and/or priming factors of basophils and mast cells.. Median concentrations of the direct allergic agonists C5a, brain-derived neurotrophic factor (BDNF), and CCL5 (RANTES) were 16.6, 41.8, and 13.9% higher, respectively, in the supernatant of apheresis PLT products that were most strongly associated with ATRs (p < 0.05 for each mediator). Other direct agonists (macrophage inflammatory protein-1α, monocyte chemotactic protein-1, eotaxin-1, interleukin-8) were similar between groups. Concentrations of acute inflammatory mediators and basophil growth and/or priming factors were also similar between groups (p > 0.2 for all associations).. The allergic agonists C5a, BDNF, and CCL5 may be mediators of ATRs in apheresis PLT products. Acute inflammatory proteins and basophil and/or mast cell growth and priming factors do not appear to be associated with apheresis PLT products that cause ATRs.

Topics: Brain-Derived Neurotrophic Factor; Chemokine CCL11; Chemokine CCL2; Chemokine CCL3; Chemokine CCL5; Complement C5a; Humans; Hypersensitivity; Inflammation Mediators; Interferon-gamma; Interleukin-6; Interleukin-8; Platelet Transfusion; Plateletpheresis; Tumor Necrosis Factor-alpha

Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell "stabilizer", is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine, leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.

Topics: Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antigen-Antibody Complex; Calcium; Cells, Cultured; Cromolyn Sodium; Dermatitis, Contact; Histamine; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-6; Interleukin-8; Leukotrienes; Mast Cells; NF-kappa B; Prostaglandin D2; Quercetin

Di-(2-ethylhexyl) phthalate (DEHP) in house dust is associated with asthma and allergic inflammatory symptoms in children. This study aimed to examine an inhibitory effect of a flavonoid apigenin on DEHP-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs). We found that apigenin significantly suppressed DEHP-stimulated expression of intercellular adhesion molecule-1 (ICAM-1) at the mRNA and protein levels and subsequently inhibited the adhesion of THP-1 monocytic cells to HUVECs. Treatment with apigenin also led to a dose-dependent inhibition of mRNA and protein expression of interleukin (IL)-6 and IL-8 in DEHP-stimulated HUVECs. Moreover, pretreatment with apigenin partially inhibited the DEHP-induced activation of c-Jun N-terminal kinase (JNK) but not the degradation of IκBα or the phosphorylation of extracellular-regulated kinase (ERK)1/2, indicating that the inhibitory effect of apigenin on the expression of IL-6, IL-8, and ICAM-1 may be mediated by JNK pathway but not IκBα/nuclear factor-κB or ERK/mitogen-activated protein kinase pathway. Furthermore, apigenin reduced the release of IL-6, IL-8, and ICAM-1 and inhibited compound 48/80-induced systemic anaphylaxis in vivo. These results suggest that apigenin can be used as a therapeutic means for the treatment of DEHP-associated allergic disorders.

Topics: Anaphylaxis; Animals; Apigenin; Cells, Cultured; Diethylhexyl Phthalate; Extracellular Signal-Regulated MAP Kinases; Female; Human Umbilical Vein Endothelial Cells; Humans; Hypersensitivity; I-kappa B Kinase; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; p-Methoxy-N-methylphenethylamine; Phosphorylation; RNA, Messenger

Translationally controlled tumor protein (TCTP) is believed to be involved in a variety of inflammatory processes: secretion of histamine and cytokines such as IL-4, IL-8, IL-13, and granulocyte/macrophage colony-stimulating factor; chemoattraction for eosinophils; augmentation of B cell proliferation; and immunoglobulin production, thereby potentially regulating allergic phenomena. In a previous study, we showed that the cytokine-releasing activity of extracellular TCTP is generated only when TCTP dimerizes via the intermolecular disulfide bond of NH(2)-terminal truncated TCTP implying that the dimerized TCTP (dTCTP) promotes the inflammatory phenomena. Modulation of dTCTP, thus, may offer a strategy for the treatment of chronic allergic diseases. In this study, we searched for dTCTP-binding peptides (dTBPs) by screening a phage-displayed 7-mer peptide library. We identified one peptide in the library, designated as dTBP2, which showed higher affinity to dTCTP than to full-length, monomeric TCTP. dTBP2 inhibited the induction of IL-8 by dTCTP from BEAS-2B cells. dTBP2 also reduced symptom score and eosinophil infiltration in a mouse rhinitis model. This study suggests that the dTBP2 binding to dTCTP modulates the release of inflammatory mediators of dTCTP. This result may provide a rational strategy for the treatment of allergic diseases.

Topics: Animals; Bacteriophages; Biomarkers, Tumor; Cytokines; Dimerization; Eosinophils; Flow Cytometry; Hypersensitivity; Inflammation Mediators; Interleukin-8; Mice; Mice, Inbred BALB C; Peptides; Tumor Protein, Translationally-Controlled 1

Fritillaria ussuriensis (FU, derived from the bulbs of various species of the genus Fritillaria, including Fritillaria thunbergii Miq.) is used in herbal medicine to treat conditions such as eczema, skin burns, and frostbite. In this study, we investigated the mechanism of the anti-allergy effect of FU. FU extract (80 mg/kg), orally administered to Sprague-Dawley (SD) rats, significantly inhibited the passive cutaneous anaphylaxis (PCA) reaction. It inhibited the compound 48/80-induced release of histamine from rat peritoneal mast cells in a concentration-dependent manner. Significant inhibitory effects of the FU extract on IL-6, IL-8, and TNF-α (1, 10, and 100 µg/mL) were observed in HMC-1 cells. Treatment with FU attenuated PMA plus A23187-induced phosphorylation of all three MAPKs, especially at concentrations of 10 and 100 µg/mL. Further, it (80 mg/kg) led to significant inhibition of mast-cell accumulation in ear tissue at the chronic phase. These results indicate that it inhibits allergic reactions.

Topics: Administration, Oral; Animals; Anti-Allergic Agents; Calcimycin; Fritillaria; Histamine Release; Hypersensitivity; Inflammation; Interleukin-6; Interleukin-8; Male; Mast Cells; Mitogen-Activated Protein Kinase Kinases; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Phosphorylation; Phytotherapy; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

We investigated the inhibitory effects of quercetin and kaempferol treatment on the suppression of immunoglobulin E (IgE)-mediated allergic responses in relation to intestinal epithelium barrier function in RBL-2H3 and Caco-2 cells.. RBL-2H3 cells as a model of intestinal mucosa mast cells were treated with flavonols followed by IgE-anti-dinitrophenyl sensitization. The extent of degranulation and the release of pro-inflammatory cytokines were measured. Caco-2 cells were stimulated with interleukin (IL)-4 or IgE-allergen with or without flavonol pretreatment and changes in the expression of CD23 mRNA and mitogen-activated protein kinase (MAPK), and chemokine release were determined.. Flavonols inhibited the secretion of allergic mediators in RBL-2H3 cells and suppressed the CD23 mRNA expression and p38 MAPK activation in IL-4 stimulated Caco-2 cells. Flavonols also suppressed IgE-OVA induced extra signal-regulated protein kinase (ERK) activation and chemokine release.. Quercetin and kaempferol effectively suppressed the development of IgE-mediated allergic inflammation of intestinal cell models.

Topics: Animals; Antioxidants; Caco-2 Cells; Chemokine CCL20; Extracellular Signal-Regulated MAP Kinases; Food Hypersensitivity; Humans; Hypersensitivity; Immunoglobulin E; Inflammation; Interleukin-8; Intestinal Mucosa; Kaempferols; Molecular Structure; p38 Mitogen-Activated Protein Kinases; Quercetin; Receptors, IgE

There is increasing evidence that daily intake of flavonoids reduced severity and prevalence of allergic diseases. However, the mechanism of its antiinflammatory effects in allergic diseases remains uncertain. Kaempferol, which belongs to the flavone group, is a strong antioxidant among natural flavonoids and is the essential component of many beverages and vegetables. Because chemokine is one of the key mediators in allergic inflammatory process, we investigated the effect of kaempferol on chemokines expression in monocytes. Our data demonstrated that kaempferol significantly inhibited the lipopolysaccharide (LPS)-induced production of monocyte-derived chemokine (MDC), interferon gamma-induced protein 10 (IP-10), and interleukin-8 (IL-8) in THP-1 cells. Growth-related oncogene-α (GRO-α) was also suppressed at a higher concentration. We also found that kaempferol was able to suppress LPS-induced mitogen-activated protein kinase (MAPK) pathways, as well as the phosphorylation of upstream c-raf and MEK1/2. In brief, kaempferol suppressed LPS-induced T helper 1 (Th1), T helper 2 (Th2), and neutrophil-related chemokines production in monocytes might be via the MAPK pathways.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Chemokine CCL22; Chemokines; Chemokines, CXC; Down-Regulation; Humans; Hypersensitivity; Interleukin-8; Kaempferols; Lipopolysaccharides; MAP Kinase Signaling System; Monocytes; Neutrophils; Osmolar Concentration; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Isoforms; Protein Kinase Inhibitors; T-Lymphocytes, Helper-Inducer

In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or FcepsilonRI-activation, and enhances FcepsilonRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-kappaB and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.

Topics: Basophils; CD28 Antigens; CD3 Complex; Cell Communication; Cell Membrane; Cells, Cultured; Complement C5a; Eosinophils; Humans; Hypersensitivity; Interleukin-1; Interleukin-1 Receptor-Like 1 Protein; Interleukin-13; Interleukin-18; Interleukin-3; Interleukin-33; Interleukin-4; Interleukin-8; Interleukins; Leukotriene C4; Neutrophils; Receptors, Cell Surface; Signal Transduction; Solubility; Th2 Cells

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Adhesion; Humans; Hypersensitivity; Interleukin-17; Interleukin-23; Interleukin-6; Interleukin-8; Major Histocompatibility Complex; Mice; Monocytes; Neutrophils; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha

Induction of proinflammatory mediators by alveolar macrophages exposed to ambient air particulate matter has been suggested to be a key factor in the pathogenesis of inflammatory and allergic diseases in the lungs. However, receptors and mechanisms underlying these responses have not been fully elucidated. In this study, we examined whether TLR2, TLR4, and the key adaptor protein, MyD88, mediate the expression of proinflammatory cytokines and chemokines by mouse peritoneal macrophages exposed to fine and coarse PM. TLR2 deficiency blunted macrophage TNF-alpha and IL-6 expression in response to fine (PM2.5), while not affecting cytokine-inducing ability of coarse NIST Standard Reference Material (SRM 1648) particles. In contrast, TLR4(-/-) macrophages showed inhibited cytokine expression upon stimulation with NIST SRM 1648 but exhibited normal responses to PM2.5. Preincubation with polymyxin B markedly suppressed the capacity of NIST SRM 1648 to elicit TNF-alpha and IL-6, indicating endotoxin as a principal inducer of cytokine responses. Overexpression of TLR2 in TLR2/4-deficient human embryonic kidney 293 cells imparted PM2.5 sensitivity, as judged by IL-8 gene expression, whereas NIST SRM 1648, but not PM2.5 elicited IL-8 expression in 293/TLR4/MD-2 transfectants. Engagement of TLR4 by NIST SRM 1648 induced MyD88-independent expression of the chemokine RANTES, while TLR2-reactive NIST IRM PM2.5 failed to up-regulate this response. Consistent with the shared use of MyD88 by TLR2 and TLR4, cytokine responses of MyD88(-/-) macrophages to both types of air PM were significantly reduced. These data indicate differential utilization of TLR2 and TLR4 but shared use of MyD88 by fine and coarse air pollution particles.

Topics: Animals; Anti-Bacterial Agents; Cell Line; Cells, Cultured; Chemokine CCL5; Humans; Hypersensitivity; Inflammation Mediators; Interleukin-6; Interleukin-8; Macrophages; Mice; Mice, Knockout; Myeloid Differentiation Factor 88; Particulate Matter; Pneumonia; Polymyxin B; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-beta1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.

Topics: Adult; Cohort Studies; Emigrants and Immigrants; Female; Humans; Hypersensitivity; Infant, Newborn; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Male; Maternal Exposure; Milk, Human; Pregnancy; Residence Characteristics; Risk Factors; Surveys and Questionnaires; Sweden; Transforming Growth Factor beta1

Rhinovirus infection is a major cause of asthma exacerbations. While rhinovirus infection is known to generate kinins in the upper respiratory track, little is known about the effect of rhinovirus on kinin generation in the lower airway. We previously identified human tissue kallikrein (hTK) as the principal lung kininogenase during allergic airway inflammation. In this report we investigate the effect of experimental rhinovirus infection on hTK activity in the airways of atopic subjects with and without asthma.. Eight atopic subjects, 4 with asthma, underwent bronchoscopy with lavage. At least 1 month later, subjects were inoculated with rhinovirus, then underwent repeat bronchoscopy with lavage 4 and 18 days later. hTK mRNA was measured in nasal scrape samples by quantitative real-time PCR. hTK activity (chromogenic substrate assay) and IL-8 levels (ELISA) were assessed in the bronchoalveolar lavage fluid.. At day 4 after rhinovirus inoculation, nasal hTK mRNA was modestly increased in both the rhinitis (1.7-fold) and asthmatic (2.1-fold) groups. A doubling or greater increase in hTK activity after rhinovirus infection was observed in all 4 asthmatic subjects (mean 19-fold increase) but only in 1 of 4 atopic subjects without asthma (mean 2-fold increase). Rhinovirus infection also increased the IL-8 protein level in bronchoalveolar lavage fluid, which correlated with hTK activity (R = 0.82).. Experimental rhinovirus infection in allergic asthmatic subjects is accompanied by increased lower airway hTK activation, which parallels the appearance of IL-8. Rhinovirus-induced hTK activation may contribute to airway inflammation and asthmatic exacerbations.

Topics: Adult; Enzyme Activation; Female; Humans; Hypersensitivity; Interleukin-8; Male; Picornaviridae Infections; Rhinovirus; RNA, Messenger; Tissue Kallikreins

Platelet activation occurs in human obstructive airway diseases and in laboratory animal models. However, there is limited evidence that platelets may be involved in equine recurrent airway obstruction (RAO) and other inflammatory diseases. This study investigated whether platelet activation also occurred in RAO.. Platelet function is altered in ponies with active RAO. This alteration can be detected ex vivo by measuring platelet adhesion.. An in vitro platelet adhesion assay measuring acid phosphatase (AcP) activity colorimetrically was adapted for use with equine platelets and responses to selected agonists were established. Platelet adhesion and aggregation was evaluated in vitro on platelets isolated from 6 ponies with RAO before, during and after a 7 h natural antigen challenge. Three ponies with no history of airway disease were also studied.. Adhesion of equine platelets to serum coated plastic was detected at concentrations of 10-100 radicaló 10(9)/l. Adhesion increased in response to stimulation with platelet activating factor and thrombin, but not equine interleukin 8. Prior to the antigen challenge, adhesion of nonstimulated platelets was low and increased significantly (P<0.05) 24 h after initiation of the challenge in RAOs, but not in the normal animals. No changes in platelet aggregation were noted in either group.. The described assay offers an alternative method to evaluate platelet function in healthy and diseased horses and can detect changes not observed using a classic aggregation assay. Circulating platelets are activated 24 h after antigen challenge of ponies with RAO and may play a role in pulmonary inflammation and/or the pathophysiology of RAO.. Investigating platelet function in RAO and airway inflammation may reveal new aspects of the pathogenesis of inflammatory lung disease in the horse.

Topics: Acid Phosphatase; Animals; Antigens; Blood Platelets; Dose-Response Relationship, Drug; Horse Diseases; Horses; Hypersensitivity; Interleukin-8; Lung Diseases, Obstructive; Platelet Activating Factor; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Thrombin

In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. AEMD decreased PMA and A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-kappaB in these effects.

Topics: Animals; Calcium; Cells, Cultured; Cytokines; Electrophoretic Mobility Shift Assay; Histamine Antagonists; Histamine Release; Hypersensitivity; Immunoglobulin E; Inflammation; Interleukin-6; Interleukin-8; Luciferases; Male; Mast Cells; Mice; Mice, Inbred ICR; Nuclear Proteins; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Plant Extracts; Rats; Rats, Sprague-Dawley; Transfection; Trees; Tumor Necrosis Factor-alpha

It has been shown that exposure in intense exposure in swine barn facilities is associated with increased respiratory symptoms and reduction in pulmonary functions. This study investigated if systemic response could be predicted by FEV(1) response following swine barn exposure.. Naïve males were tested at baseline, low and high endotoxin and dust levels. Subjects were classified as "more responsive" (n = 9) or "less responsive" (n = 11) based on FEV(1) reduction following high endotoxin exposure. Health measures included pulmonary function testing, blood samples and nasal lavage. Environmental samples were collected from the barn.. White blood cells and blood lymphocytes at low exposure were significantly greater in those who were "more responsive" compared to those who were "less responsive". There was a significant increase in blood lymphocytes, serum IL6, total nasal lavage cells and nasal IL8 at high exposure among "more responsive" subjects compared to "less responsive" subjects.. Respiratory response to high-level endotoxin and dust exposure predicts evidence of inflammatory response throughout a range of endotoxin and dust exposures.

Topics: Adolescent; Adult; Air Pollutants, Occupational; Animal Husbandry; Animals; Biomarkers; Cross-Over Studies; Dust; Endotoxins; Housing, Animal; Humans; Hypersensitivity; Interleukin-6; Interleukin-8; Male; Occupational Exposure; Respiratory Function Tests; Respiratory Tract Diseases; Statistics, Nonparametric; Swine

Allergic rhinitis is characterized by a T(H)2-dependent inflammation. Nasal obstruction is a typical symptom of allergic rhinitis.. To evaluate the possible relationships among nasal symptoms, allergic inflammation, including inflammatory cells and cytokine pattern, and nasal airflow in children with seasonal allergic rhinitis.. Children with seasonal allergic rhinitis and moderate-severe nasal obstruction were evaluated during the pollen season. Total symptom score, rhinomanometry, nasal lavage, and nasal scraping were evaluated in all patients. Inflammatory cells were counted by conventional staining; interleukin 5 (IL-5) and IL-8 levels were measured by immunoassay on fluids recovered from nasal lavage.. Twenty children (11 boys and 9 girls; mean +/- SD age, 12.9 +/- 1.7 years) participated in this study. Eosinophil levels were significantly associated with total symptom score (r = 90.6%, P < .001), IL-5 (r = 94.9%, P < .001), and nasal flow (r = -93.6%, P < .001). No association was elicited with IL-8 (r = 9.4%, P = .69). In a multivariate analysis that included eosinophils, neutrophils, and IL-5, eosinophil levels were shown to be the only independent predictor of nasal flow.. This study demonstrates the close connection between T(H)2 cytokines and eosinophil infiltration. In addition, there is clear evidence concerning the relationship among nasal symptoms, eosinophil infiltration, and nasal airflow. These findings constitute evidence of the relationship between nasal airflow impairment and eosinophilic inflammation in children with seasonal allergic rhinitis.

Topics: Child; Eosinophils; Female; Humans; Hypersensitivity; Inflammation; Interleukin-5; Interleukin-8; Male; Nasal Lavage Fluid; Nasal Obstruction; Nose; Pulmonary Ventilation; Rhinitis, Allergic, Seasonal; Skin Tests; Th2 Cells

Intestinal epithelial cells (IEC) are hyporesponsive to LPS. Responsiveness to luminal bacteria has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). In support of this, previous studies have demonstrated that some intestinal epithelial cell lines are induced by IFN-gamma to respond to LPS. However, both the responsiveness to LPS and the effect of IFN-gamma in intestinal cell lines are heterogeneous. In addition, IFN-gamma may be sequestered in the extracellular matrix (ECM) compartment. The ECM-bound form is more effective than soluble IFN-gamma in producing its biological effects in several experimental models. We investigated the effect of ECM-bound and soluble IFN-gamma treatment on interleukin-8 (IL-8) secretion in response to LPS in freshly isolated villous and crypt cells. We demonstrate that ECM-bound, but not soluble IFN-gamma, induced an increase in IL-8 secretion in response to LPS in undifferentiated crypt cells. This effect was associated with an increase in TLR4 expression. In contrast, mature villous cells did not modify their response to LPS when treated with IFN-gamma (ECM-bound or soluble). These results suggest that selective changes in immature crypt cells induced by IFN-gamma bound to extracellular matrix could contribute to inappropriate responsiveness to commensal bacteria in IBD.

Topics: Animals; Cells, Cultured; Epithelial Cells; Extracellular Matrix; Hypersensitivity; Interferon-gamma; Interleukin-8; Intestines; Lipopolysaccharides; Membrane Glycoproteins; Protein Binding; Receptors, Cell Surface; Swine; Toll-Like Receptor 4; Toll-Like Receptors

Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of COX-2 expression is responsible for increased PG release during inflammatory conditions and is thought to be also involved in allergic states. In this study, we demonstrate that in human T, B and natural killer lymphocytes from allergic patients, COX-2 expression became induced upon cell challenge with specific allergens and that this process is presumably IgE dependent and occurs after CD23 receptor ligation. This induction took place at both mRNA and protein levels and was accompanied by PGD2 release. IgE-dependent lymphocyte treatment elicited, in parallel, an activation of the MAPK p38 and extracellular signal-regulated kinase 1/2, an enhancement of calcineurin (CaN) activity, and an increase of the DNA-binding activity of the nuclear factor of activated T cells and of NF-kappaB, with a concomitant decrease in the levels of the cytosolic inhibitor of kappaB, IkappaB. In addition, specific chemical inhibitors of MAPK, such as PD098059 and SB203580, as well as MG-132, an inhibitor of proteasomal activity, abolished allergen-induced COX-2 up-regulation, suggesting that this process is mediated by MAPK and NF-kappaB. However, induction of COX-2 expression was not hampered by the CaN inhibitor cyclosporin A. We also examined the effect of a selective COX-2 inhibitor, NS-398, on cytokine production by human lymphocytes. Treatment with NS-398 severely diminished the IgE-dependently induced production of IL-8 and TNF-alpha. These results underscore the relevant role of lymphocyte COX-2 in allergy and suggest that COX-2 inhibitors may contribute to the improvement of allergic inflammation through the reduction of inflammatory mediator production by human lymphocytes.

Topics: Allergens; Cells, Cultured; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; DNA-Binding Proteins; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-8; Membrane Proteins; Mitogen-Activated Protein Kinases; NF-kappa B; NFATC Transcription Factors; Nuclear Proteins; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; T-Lymphocyte Subsets; Transcription Factors; Tumor Necrosis Factor-alpha; Up-Regulation

The amniotic membrane (AM), which is the innermost layer of the placenta, was shown to possess anti-inflammatory and anti-fibrotic properties in various in vitro and clinical studies.. To evaluate the anti-fibrotic and anti-inflammatory effects of the AM matrix (AMM) on human conjunctival and lung fibroblasts in an in vitro system that tests fibrotic and inflammatory responses at the effector stages of allergic inflammation.. Human conjunctival or lung fibroblasts were seeded on plastic or on the stromal aspect of the AM, which was mounted on plastic inserts. Sonicates of human peripheral blood eosinophils activated with lipopolysaccharide (LPS), or human mast cell (HMC-1) leukaemia cell sonicates, were added to sub-confluent fibroblast monolayers. Proliferation of the sub-confluent fibroblasts was assessed using the [3H]-thymidine incorporation assay. The production of transforming growth factor (TGF)-beta1, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-8 in conjunctival or lung fibroblasts was measured in conditioned media from these cultures by ELISA.. After 4 days in culture, the [3H]-thymidine incorporation assay indicated a reduced proliferation of activated conjunctival and lung fibroblasts when cultured directly on the AMM. The production of both TGF-beta1 and IL-8 was significantly suppressed in activated conjunctival fibroblasts cultured on the AMM compared with those cultured on plastic, while the production of both TGF-beta1 and GM-CSF was decreased in human lung fibroblast cultured on the AMM.. The AMM is capable of suppressing fibrotic responses in an in vitro system of effector stages of ocular allergic inflammation. These data may provide a basis for exploring matrix components in the AM for the treatment of allergic eye disease.

Topics: Amnion; Cell Adhesion; Cell Division; Cell Survival; Cells, Cultured; Conjunctiva; Down-Regulation; Eosinophils; Fibroblasts; Fibrosis; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypersensitivity; Inflammation; Interleukin-8; Lung; Mast Cells; Transforming Growth Factor beta

To observe the effect on infantile allergic cough with Minkeqing oral liquid (Minkeqing) and to study its cell molecular biologic mechanism.. The rat model was induced by inhalating ovalbumin; then the effects of Minkeqing on IL-6, IL-8, ET-1, TX-B2 in the blood and the bronchoalveolar lavage fluid (BALF) of the animal model were observed.. Minkeqing could reduce the levels of IL-6,IL-8,ET-1,Tx-B2 in the blood and BALF of the animal model.. Minkeqing has the significant function of inhibiting the release of inflammatory mediums.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cough; Drug Combinations; Drugs, Chinese Herbal; Endothelin-1; Hypersensitivity; Interleukin-6; Interleukin-8; Male; Ovalbumin; Plants, Medicinal; Random Allocation; Rats; Rats, Wistar; Thromboxane B2

Sodium/potassium (Na/K) ratios are considered to be a marker of mammary epithelial paracellular permeability. The aim of the present study was to investigate the association between maternal atopy and Na/K ratios in breast milk and the association between Na/K ratios in breast milk and the development of atopy in the offspring. Early and mature milk samples were obtained from 30 atopic and 43 non-atopic women. We found no differences in the Na/K ratios between atopic and non-atopic women. At 18 months of age, 22 (30%) of the children had a positive skin prick test (SPT) and 26 (36%) had symptoms of atopic diseases. Overall, high levels of Na/K compared with low and slightly raised levels of Na/K in the maternal milk tended to be associated with a positive SPT and atopic disease. However, if the mother was atopic, high levels of Na/K in early or mature milk were associated with a significantly increased risk of a positive SPT or atopic disease in the offspring [RR = 4.8 (1.9-12)] whereas no such association was observed in non-atopic mothers [RR = 0.8 (0.4-1.7), p for interaction = 0.001]. Thus, high Na/K levels in the breast milk may be associated with the development of atopy and atopic diseases in the offspring of atopic mothers.

Topics: Age Factors; Cell Membrane Permeability; Epithelial Cells; Female; Humans; Hypersensitivity; Immunoglobulin A, Secretory; Infant; Infant, Newborn; Interleukin-8; Mammary Glands, Human; Milk, Human; Potassium; Skin Tests; Sodium; Time Factors

We examined whether the common crop mycotoxin deoxynivalenol (DON) from Fusarium species is toxic to human colonic (Caco-2), lung (A549) and monocytic (U937) cell lines. Moreover, since DON reportedly induces increased levels of Th2 cytokines and total IgE, and we have observed that mould extracts adjuvated allergy development in mice, possible adjuvant effect of DON on allergy was studied in a mouse model. For all the cells, exposure to DON for 24 h reduced cellular protein synthesis, proliferation and survival rate dose-dependently. In addition, production of IL-8 in the U937 cell line increased up to eight-fold at levels of DON just lower than the most toxic one, suggesting that IL-8 can be used as an additional index for cytotoxicity in mononuclear phagocytes. However, DON did not increase levels of allergen-specific IgE or IgG1 in the mouse model for allergy. These results suggest that DON, when inhaled or ingested, may have toxic effect on human alveolar macrophages and epithelial cells in lungs and colon, but does not increase the allergic response to allergens.

Topics: Adjuvants, Immunologic; Animals; Caco-2 Cells; Cell Division; Cell Line, Tumor; Cell Survival; Colon; Female; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-8; Lung; Lymph Nodes; Mice; Mice, Inbred BALB C; Monocytes; Protein Biosynthesis; Trichothecenes; U937 Cells

The aim of the study was to assess the prevalence of work-related symptoms in hop growers and their relation to bioaerosols exposure. The study group comprised 69 hop growers and 58 office workers as controls. The examination included: physician-administrated questionnaire, PEF measurements, skin prick test, agar-gel precipitation test, and migration inhibition test. Microbiological air sampling was performed on all farms.. The concentrations of total airborne microflora ranged from 2.08 to 129.6 x 10(3) CFU/m3. Airborne endotoxin and dust concentrations ranged from 26 to 6250 ng/m3 and 0.2-31.7 mg/m3, respectively. Altogether 52.2% of farmers complained of work-related symptoms. Positive skin reactions to microbial allergens were significantly more frequent in a group of hop growers with work-related respiratory symptoms compared to the rest of the farmers (18% vs 2%, P <0.05). Positive reactions in agar-gel precipitation test and in the leukocyte migration inhibition test were not correlated with the occurrence of work-related symptoms. The mean daily PEF values in farmers were lower compared to controls (469.7 +/- 127.5 vs 562.9 +/- 123.8; P <0.001). PEF (amp%mean) was higher in farmers compared to controls (9.3% vs 8.1%; P <0.05).. Despite relatively lower exposure to bioaerosols, compared to farmers in other branches of agriculture, over 50% of hop growers complained of work-related symptoms. This may be partly due to the effects of microbial allergens and toxins and partly to the irritant or allergic properties of hop plant itself.

Topics: Adolescent; Adult; Aerosols; Aged; Aged, 80 and over; Air Pollutants, Occupational; Colony Count, Microbial; Endotoxins; Female; Humans; Humulus; Hypersensitivity; Interleukin-6; Interleukin-8; Male; Middle Aged; Occupational Diseases; Occupational Exposure; Poland; Prevalence; Respiratory Function Tests; Skin Tests; Surveys and Questionnaires; Tumor Necrosis Factor-alpha

The T helper type-2 (Th2)-dominated situation can be observed in allergic diseases such as asthma or atopic dermatitis. A reduced ability to produce IL-12, which is a key cytokine for the induction of Th1 responses, has been proposed to lead to aberrant Th2 development in these disease conditions.. This study was intended to examine how IL-12-producing ability might associate with allergic diseases as a function of age.. IL-12 production by monocytes at various ages was assessed in patients with bronchial asthma and/or atopic dermatitis (n = 100) in comparison with non-allergic control subjects (n = 144). Whole blood cells were stimulated with lipopolysaccharide (LPS) after priming with IFN-gamma, then intracellular cytokine expression of IL-12 and IL-8 as a control cytokine of CD14-positive cells was assessed by flow cytometric analysis.. In the control subjects, the ability of monocytes to produce IL-12 was negligible at birth and gradually increased with advancing age, whereas IL-8 production was intense throughout the human life. At more than 7 years of age, IL-12 production of patients with allergic diseases was significantly lower compared with that of control subjects. The unexpected finding was that infants and children below 6 years of age with allergic diseases tended to produce more IL-12 compared with age-matched controls. In this young group, it was noted that enhanced IL-12 production by monocytes was especially observed in allergic patients with specific IgE antibodies against some food allergens. Significant inverse relationships between serum IgE levels and IL-12-producing ability were found in the teenage and adult groups, but not in the younger children.. IL-12 appeared to play different roles in the pathogenesis of allergic diseases between younger and older ages.

Topics: Adolescent; Adult; Aging; Asthma; Child; Child, Preschool; Dermatitis, Atopic; Female; Flow Cytometry; Humans; Hypersensitivity; Infant; Infant, Newborn; Interferon-gamma; Interleukin-12; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; T-Lymphocytes; Th1 Cells; Th2 Cells

Eosinophils are seen at sites of inflammation in diseases such as helminthic infestation, asthma, ulcerative colitis and some neoplastic diseases. They are also associated with connective tissue remodelling, for example in longstanding asthma. In the present study, we investigated whether eosinophils express the CXC chemokine epithelial cell-derived neutrophil activating peptide (ENA-78/CXCL5), a chemokine that can activate neutrophils and in addition possesses angiogenic properties. Immunocytochemistry detected CXCL5 in eosinophils and the peptide was localized in the specific granules by immunoelectron microscopy.. In eosinophil lysates, 12 +/- 2 pg (mean +/- SEM) of CXCL5 was detected per 106 cells by enzyme-linked immunosorbent assay (ELISA). Weak constitutive expression of CXCL5, as well as the related CXC chemokine IL-8/CXCL8, could be detected in freshly isolated eosinophils by RT-PCR. However, during prolonged incubation of eosinophils, a strong increase in both CXCL5 and IL-8/CXCL8 expression was seen, as detected by RT-PCR, and increasing amounts of CXCL5 peptide with time were detected in the incubation medium by ELISA. Addition of TNF-alpha neutralizing antibodies during prolonged incubation significantly inhibited CXCL5 production, demonstrating involvement of auto- and paracrine effects from TNF-alpha produced by eosinophils themselves. Addition of IFN-gamma showed a strong inhibitory effect on CXCL5 synthesis.. These findings suggest that, through expression of CXCL5, eosinophils can recruit and activate CXC receptor 2 (CXCR2)-bearing cells such as neutrophils at sites of inflammation. Eosinophils may also promote connective tissue remodelling through release of this peptide.

Topics: Cells, Cultured; Chemokine CXCL5; Chemokines, CXC; Culture Media, Conditioned; Eosinophils; Gene Expression; Humans; Hypersensitivity; Immunohistochemistry; In Situ Hybridization; Interleukin-1; Interleukin-8; Microscopy, Immunoelectron; Neutrophil Activation; Reverse Transcriptase Polymerase Chain Reaction; RNA; Tumor Necrosis Factor-alpha

Accumulating data show that fibroblasts are important regulators in the development and maintenance of allergic airway inflammation. However, most studies so far have used individual recombinant cytokines in high concentrations, unlikely to be found in vivo. We aimed to investigate how cytokines produced by peripheral blood mononuclear cells (PBMC) affect fibroblast functions. Primary airway fibroblasts where incubated with allergen-stimulated or non-stimulated PBMC supernatants from allergic patients. The levels of cytokines in PBMC supernatants were measured and the expression of CD54, CD40 and CD106 as well as the production of eotaxin, interleukin (IL)-6 and IL-8 were assessed in fibroblasts. Although the levels of single cytokines measured in PBMC supernatants were low, a significant up-regulation of the surface molecules as well as of IL-6 and IL-8 production was found in fibroblasts cultured with allergen-stimulated PBMC supernatants as compared to non-stimulated, while the increase in eotaxin production was not significant. The evaluation of correlations between cytokines produced by PBMC and effects seen on fibroblasts did not indicate a crucial role for any single cytokine. Furthermore, the addition of comparably low concentrations of recombinant interferon (rIFN)-gamma or recombinant tumour necrosis factor (rTNF)-alpha did not induce the same effects as PBMC supernatants, the only exception being TNF-alpha as a direct inducer of CD54 expression. Our results show that synergistic mechanisms has a more important role than single mediators, highlighting important differences between in vitro experiments, where effects of individual mediators are studied, versus the actual situation in vivo.

Topics: Cells, Cultured; Cytokines; Fibroblasts; Humans; Hypersensitivity; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-13; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lymphocyte Activation; Nasal Polyps; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Eosinophils are a major component of the inflammatory response in persistent airway inflammation in asthma. The factors that determine the retention of eosinophils in the airway remain poorly understood. Elevated levels of fibronectin have been observed in the airway of patients with asthma, and the levels correlate with eosinophil numbers. To determine if fibronectin density modulates eosinophil function, we investigated the effect of fibronectin and vascular cell adhesion molecule 1 (VCAM-1) density on eosinophil migration and signaling via the p38 and extracellular regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) signaling pathways. There was a dose-dependent inhibition of eosinophil spreading and migration on increasing concentrations of fibronectin but not VCAM-1. In addition, activation of p38 MAPK was inhibited at high fibronectin but not high VCAM-1 concentrations, and ERK activity was slightly reduced at high VCAM-1 and fibronectin concentrations. Together, the results demonstrate that fibronectin but not VCAM-1 inhibits eosinophil migration and signaling.

Topics: Adult; Cell Adhesion; Cell Movement; Cell Polarity; Cell Size; Chemokine CCL11; Chemokine CCL5; Chemokines, CC; Chemotaxis, Leukocyte; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Activation; Eosinophils; Fibronectins; Humans; Hypersensitivity; Interleukin-5; Interleukin-8; MAP Kinase Signaling System; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; N-Formylmethionine Leucyl-Phenylalanine; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Processing, Post-Translational; Vascular Cell Adhesion Molecule-1

In addition to its more widely recognized role in promoting IgE synthesis, we speculate that interleukin-4 (IL-4) may modulate both allergic- and nonallergic-type inflammatory processes in the airway mucosa. We examined in vivo the effect of IL-4 on granulocyte and cytokine homeostasis in the nasal airways of nonallergic volunteers. Ten (N = 10) healthy subjects received nasal IL-4 (10 microg) or saline (0.9%) challenges on separate occasions. Nasal lavage was obtained before and 24 h after nasal challenges. We report that IL-4 induced a significant increase in IL-6 and produced elevated levels of eosinophils and neutrophils compared to saline. These data demonstrate that IL-4 can modulate both allergic- and nonallergic-type inflammatory responses in the nasal airways of nonallergic individuals.

Topics: Adolescent; Adult; Eosinophils; Humans; Hypersensitivity; Inflammation; Interleukin-4; Interleukin-6; Interleukin-8; Middle Aged; Nasal Mucosa

The prevalence of respiratory allergies has increased over the last 20 years, highlighting the need for a simple and noninvasive tool to investigate, in a clinical and epidemiological context, airway-inflammation mechanisms encountered in allergic and inflammatory processes. The nose, as the first region of the respiratory tract to come in contact with airborne pollutants, is easily explored with the use of nasal lavage (NL). We evaluated an NL method for adults and children, along with its reproducibility and capacity to separate different subgroups. NL reproducibility, assessed in 10 healthy, nonsmoking adults on three different occasions, was determined with the use of the intraclass coefficient of correlation for such inflammatory markers as total cell count, albumin, urea, neutrophil elastase, alpha(1)-antitrypsin, interleukin-6, and interleukin-8. Using this NL method, we analyzed nasal markers of 50 healthy adults (smokers and nonsmokers) and 12 healthy children. Our NL method demonstrated high reproducibility with regard to total cell count, albumin, urea, and alpha(1)-antitrypsin (intraclass correlation coefficient > 0.75). Compared with NL results in nonsmokers, NL in heavy smokers revealed significant increased concentrations of total cell counts and interleukin-8 and significant decreased concentrations of interleukin-6. These findings suggest that NL can be used as a tool in the assessment of inflammation because it has the correct reproducibility and can discriminate between heavy smokers and nonsmokers. Moreover, the use of this standardized method in children is feasible.

Topics: Adolescent; Adult; Albumins; alpha 1-Antitrypsin; Biomarkers; Cell Count; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypersensitivity; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Nasal Lavage Fluid; Neutrophils; Reproducibility of Results; Respiratory Tract Diseases; Urea

IL-10 exhibits anti-inflammatory effects on activated rodent mast cells (MC) in vitro and inhibits allergen-induced airway inflammation in vivo in murine models. The effects of IL-10 on the allergic activation of human MC are presently unknown.. In light of the well-known heterogeneity of mast cell reactivity between animal species, one cannot readily predict the response of human MC to IL-10. Moreover, the impact of IL-10 on MC-derived proinflammatory mediators is still unknown. Thus, the objective of this study was to investigate the effects of IL-10 on the release of inflammatory mediators by IgE/anti-IgE-challenged human cord blood-derived mast cells (CBMC), used as an in vitro model of MC phenotypically similar to human lung MC.. Highly purified human MC were obtained by a first step of long-term culture of cord blood mononuclear cells in the presence of human recombinant stem cell factor (rhSCF) and of human recombinant IL-6 (rhIL-6), followed by a second step of purification by depletion of contaminating cells with an immunomagnetic. The cells were treated with human IgE, then challenged with anti-human IgE, in the presence or the absence of recombinant rhIL-10 used at various concentrations. Histamine, tumour necrosis factor-alpha (TNF-alpha), IL-5 and IL-8 were measured in the various supernatants collected at different times after the beginning of the challenge.. IL-10 inhibited the release of TNF-alpha and of IL-8, but not of IL-5, by activated CBMC. Interestingly, IL-10 also inhibited the release of histamine by activated CBMC, contrasting with data reported for rodent MC.. These findings suggest that IL-10 might have anti-inflammatory effects on IgE/anti-IgE-challenged human MC by inhibiting their release of TNF-alpha, IL-8 and histamine. These data provide new insights into the control of human mast cell activation and might lead to a better knowledge of the cellular mechanisms controlling allergic reactions.

Topics: Cell Culture Techniques; Cell Survival; Dose-Response Relationship, Immunologic; Fetal Blood; Histamine Release; Humans; Hypersensitivity; Immunoglobulin E; Inflammation Mediators; Interleukin-10; Interleukin-5; Interleukin-8; Mast Cells; Recombinant Proteins; Time Factors; Tumor Necrosis Factor-alpha

A series of nicotinamide N-oxides was synthesized and shown to be novel, potent, and selective antagonists of the CXCR2 receptor. Furthermore, these compounds showed significant functional activity against GRO-alpha-driven human neutrophil chemotaxis. Compounds of this class may be useful for the treatment of inflammatory, auto-immune, and allergic disorders.

Topics: Autoimmune Diseases; Binding Sites; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Chemotaxis; Growth Substances; Humans; Hypersensitivity; Inflammation; Inhibitory Concentration 50; Intercellular Signaling Peptides and Proteins; Interleukin-8; Neutrophils; Niacinamide; Protein Binding; Receptors, Interleukin-8B; Structure-Activity Relationship

Topics: Anti-Inflammatory Agents; Butyrophenones; Cells, Cultured; Cetirizine; Chymases; Eosinophils; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Histamine; Histamine H1 Antagonists; Humans; Hypersensitivity; Intercellular Adhesion Molecule-1; Interleukin-3; Interleukin-8; Loratadine; Mast Cells; Piperidines; Potassium Channel Blockers; Potassium Channels; Prostaglandin D2; Pyridines; Recombinant Fusion Proteins; Recombinant Proteins; Serine Endopeptidases; Terfenadine; Time Factors; Tryptases

The organic compounds of diesel exhaust particles (DEP-PAHs) have been shown to favor immunoglobulin production and bronchial hyperresponsiveness and to affect cytokine and chemokine productions. To evaluate if diesel exhaust could act in synergy with a house dust mite allergen (Der p 1), peripheral blood mononuclear cells from allergic patients were exposed to DEP-PAHs, with or without purified Der p 1. DEP-PAHs and Der p 1 separately induced an increase in interleukin (IL)-8, regulated on activation, normal T cells expressed and secreted (RANTES), and tumor necrosis factor-alpha concentrations. Interestingly, a synergy between the two stimuli was also observed. In the case of monocyte chemotactic protein (MCP)-1, DEP-PAHs reduced the release, whereas Der p 1 enhanced it. A simultaneous exposure led to reduced production as compared with allergen exposure alone, but still represented an increase as compared with the control exposure. Mitogen-activated protein (MAP) kinase Erk1/2 antagonist mainly inhibited the release of MCP-1, whereas MAP kinase p38 antagonist mainly suppressed the release of IL-8 and RANTES. Messenger RNA expression correlated with protein measurements. Moreover, supernatants from cells exposed to both DEP-PAHs and Der p 1 had a significant chemotactic activity on neutrophils and eosinophils. These findings suggest that simultaneous exposure of allergic patients to DEPs and allergens could result in high local chemokine levels via MAP kinase pathways activation, increasing the likelihood of reaching a critical threshold leading to the initiation of respiratory allergic symptoms.

Topics: Antigens, Dermatophagoides; Cell Survival; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemokines; Chemotaxis; Child, Preschool; Culture Media, Conditioned; Cytokines; Drug Synergism; Enzyme Inhibitors; Flavonoids; Glutathione; Glycoproteins; Humans; Hypersensitivity; Imidazoles; Interleukin-8; Leukocytes, Mononuclear; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Pyridines; Reactive Oxygen Species; RNA, Messenger; Tumor Necrosis Factor-alpha; Vehicle Emissions

Segmental allergen challenge is a powerful tool to study inflammatory reactions in asthmatic airways. There is little information on the early events at 5 min and 4 h after allergen challenge with respect to the cell influx and the chemokine interleukin-8 (IL-8).. Seven mild to moderate allergic asthmatics (AA group), 5 allergic nonasthmatics (ANA group) and 5 nonallergic controls underwent segmental allergen challenge, with allergen doses based upon skin reactivity. Bronchoalveolar lavage (BAL) samples were obtained before, 5 min and 4 h postchallenge, and were analyzed for cell numbers and differential counts, eosinophil and neutrophil chemotactic activity, and levels of IL-8.. At 5 min postchallenge, no changes were observed compared to baseline. At 4 h postchallenge, an increase was found in the number of neutrophils and the levels of IL-8, which was dependent on the dose of allergen in the AA and ANA group. At the same allergen dose, the increases in neutrophils and levels of IL-8 were calculated to be 91 and 67 times higher, respectively, in AA than in ANA. Levels of IL-8 correlated with the number of neutrophils and with the in vitro neutrophil chemotactic activities in BAL fluid.. Neutrophil chemotactic activity is increased in BAL fluid at 4 h after segmental allergen challenge. We suggest that apart from IgE-mediated mast cell degranulation, additional local factors in the airways determine the degree of IL-8 increase and neutrophil influx.

Topics: Adult; Allergens; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Cell Count; Chemotaxis, Leukocyte; Eosinophils; Female; Humans; Hypersensitivity; Interleukin-8; Lipopolysaccharides; Male; Neutrophils; Skin Tests

Topics: Anti-Bacterial Agents; Asthma; Clarithromycin; Eosinophils; Erythromycin; Fosfomycin; Humans; Hypersensitivity; Immunosuppressive Agents; In Vitro Techniques; Interleukin-8; Josamycin; Tacrolimus

Candidiasis is the most commonly encountered opportunistic infection among HIV-positive subjects. The purpose of this study was to assess specific keratinocyte immune parameters in the pseudomembranous and erythematous forms of HIV-associated oral candidiasis.. This collaborative study from three centers analyzed 25 HIV-positive and 10 HIV-negative subjects with either pseudomembranous or erythematous candidiasis. Oral biopsy specimens from lesional tissues were procured, and histopathologic features were correlated with immunohistochemical and in situ hybridization investigations for the expression of interleukin 1 alpha, interleukin 8, antimicrobial calprotectin, lymphocyte populations, and Candida antigen.. Both pseudomembranous and erythematous candidiasis among HIV-infected subjects showed a mild interface lymphocytic mucositis with the presence of neutrophilic subcorneal abscesses in the latter. Erythematous candidiasis cases that failed to show surface mycelia, did yield positive results for Candida antigens in the parakeratinized layer. The expression of inflammatory chemokines were positive in all groups and calprotectin appeared to serve as a keratinocyte barrier to hyphal penetration.. The erythematous form of candidiasis is often devoid of hyphae yet the presence of Candida antigens in the surface epithelium implicates an immune or allergic process. The intactness of chemokines and antimicrobial calprotectin in keratinocytes may explain why disseminated candidiasis is rarely encountered in HIV-infected patients.

Topics: AIDS-Related Opportunistic Infections; Antigens, Fungal; Antigens, Surface; Calcium-Binding Proteins; Candida; Candidiasis, Oral; Chemokines; Erythema; Gene Expression Regulation; Gene Expression Regulation, Fungal; HIV Seronegativity; HIV Seropositivity; Humans; Hypersensitivity; Immunohistochemistry; In Situ Hybridization; Interleukin-1; Interleukin-8; Keratinocytes; Leukocyte L1 Antigen Complex; Lymphocytes; Mouth Mucosa; Neural Cell Adhesion Molecules; Neutrophils; Stomatitis

In studies of disease processes, increasing knowledge leads to an increased awareness of the complexity of the underlying mechanisms. The intense research activity in the chemokine field has made this acutely manifest. Numerous chemokines have been discovered through the use of (1) bioassay of in vitro cell culture supernatants and in vivo exudates from animal models of inflammation and (2) molecular biology techniques. Any one chemokine can often be produced by a number of different cell types and exert its effects on different target cells. This has been interpreted by some as implying a high degree of redundancy. Although this is understandable, in disease processes parallel and sequential mechanisms are possible, and potentially important therapeutic targets have emerged. There is compelling evidence from animal and clinical studies that eosinophils are important effector cells in asthma, but this relationship is as yet unproven in the human disease. Two possible targets to prevent eosinophil recruitment to the lung are IL-5 and its receptor, which are important in several aspects of eosinophil biology, and eotaxin and its receptor, CCR3. The eotaxin receptor is particularly attractive as a target as it is expressed in high numbers on eosinophils, but not other leukocytes, and appears to be the major detector of the eosinophil for eotaxin and other chemokines such as MCP-4. Eotaxin and CCR3 knockout mice are being developed, and animal models will continue to be invaluable when antagonists are available. In the shape of receptor antagonists, the chemokine field may yet provide the final proof of concept for the long-established eosinophil theory of asthma in humans.

Topics: Amino Acid Sequence; Animals; Asthma; Bronchoalveolar Lavage Fluid; Chemokine CCL11; Chemokine CCL2; Chemokine CCL5; Chemokines; Chemokines, CC; Chromatography, High Pressure Liquid; Cytokines; Disease Models, Animal; Endothelium, Vascular; Humans; Hypersensitivity; Interleukin-8; Leukocytes; Molecular Sequence Data; Ovalbumin

Interleukin-8 (IL-8) is a cytokine with potent neutrophil chemotactic and activating properties and is active in inflammatory conditions in man. It has been identified in human inflammatory skin conditions where it is likely to be responsible for both neutrophil recruitment from the circulation and possibly T-lymphocyte chemoattraction. Studies in animals also suggest that IL-8 may augment skin oedema.. To study the effects of intradermally administered IL-8 in humans on tissue oedema and cellular recruitment in atopic and non-atopic volunteers.. Interleukin-8 (1.2 x 10(-7) M) in the presence and absence of histamine was administered by intradermal injection. Wheal and erythema area were measured at regular intervals and 3 h following challenge punch biopsies were taken for immunocytochemistry. Cellular infiltrate was measured by immunocytochemical identification of neutrophils, eosinophils and T-lymphocytes in glycol-methacrylate-embedded sections.. In the presence of histamine, IL-8 provoked a significantly greater wheal area when compared to that produced by histamine alone (P < 0.001). In the presence of histamine, IL-8 produced a significantly greater neutrophil infiltrate (P < 0.05), however, neither lymphocyte or eosinophil infiltration was found to be increased with IL-8 challenge. There was no difference observed between atopic and non-atopic subjects, nor were any effects of IL-8 demonstrated in the absence of histamine.. This study demonstrates that in human skin, IL-8 induces increased microvascular permeability and neutrophil infiltration, but not eosinophil or T-lymphocyte chemoattraction.

Topics: Adolescent; Adult; Allergens; Capillary Permeability; Chemotaxis, Leukocyte; Edema; Eosinophils; Histamine; Humans; Hypersensitivity; Immunohistochemistry; Injections, Intradermal; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Neutrophils; Recombinant Proteins; Skin Diseases; T-Lymphocytes

1. The role of platelet activating factor (PAF) in neutrophil infiltration in air pouch type allergic inflammation in rats was investigated. 2. Neutrophil infiltration into the pouch fluid 8 h after injection of the antigen (azobenzenearsonate-conjugated acetyl bovine serum albumin) solution into the air pouch of immunized rats was inhibited dose-dependently by treatment with PAF antagonists (CV-3988, L-652,731 and Y-24,180) in parallel with the decrease in neutrophil chemotactic activity in the pouch fluid. 3. Four hours after injection of the antigen solution into the air pouch of immunized and non-immunized rats, there was no significant difference between the two groups in the number of total leucocytes, neutrophils, mononuclear cells and eosinophils in the pouch fluid. However, when the infiltrated leucocytes were incubated in medium, chemotactic factor production by leucocytes from immunized rats was greater than that from non-immunized rats. 4. When leucocytes from non-immunized rats were preincubated for various periods in the medium containing 10 or 50 nM of PAF, washed, and further incubated in the medium containing no PAF, chemotactic factor production was not stimulated. 5. The increase in the chemotactic activity in the conditioned medium was not suppressed by the 5-lipoxygenase inhibitor, AA861. In addition, the chemotactic activity in the conditioned medium was not inhibited by the PAF antagonists. 6. Incubation of the infiltrated leucocytes in the medium containing the protein synthesis inhibitor, cycloheximide, inhibited chemotactic factor production in a concentration-dependent manner in parallel with the decrease in uptake of [3H]-leucine into the acid-insoluble fraction of leucocytes. 7. Separation of the chemotactic activity in the conditioned medium by isoelectric focusing revealed that the leucocyte infiltrated into the pouch fluid produce two kinds of factors, viz. leucocyte-derived neutrophil chemotactic factor-i (LDNCF-1) and LDNCF-2 of which pI values are 4-5 and above 8,respectively.8. The results indicate that PAF has no significant role in leucocyte activation to produce chemotactic factors, and that neutrophil chemotactic factors produced by infiltrated leucocytes are not PAF or leukotriene B4 but are produced through a protein synthesis mechanism.9. The mechanism of action of PAF antagonists on neutrophil infiltration into the inflammatory locus is discussed.

Topics: Animals; Azepines; Benzoquinones; Cells, Cultured; Culture Media, Conditioned; Dose-Response Relationship, Drug; Furans; Hypersensitivity; Immunization; Interleukin-8; Isoelectric Focusing; Leukocytes; Lipoxygenase Inhibitors; Phospholipid Ethers; Platelet Activating Factor; Rats; Triazoles

The objective of this study was to investigate the effect of interleukin-8 (IL-8) and RANTES on basophil histamine release induced with monocyte chemoattractant peptide-1 (MCP-1) and crude histamine releasing factor (HRF). IL-8 induced low levels of histamine release (8.5 +/- 0.5%) from basophils obtained from only six of 20 donors at high concentrations (10(-6) M). RANTES induced histamine release (16 +/- 2%) from basophils of four of 15 donors at 10(-7) M concentration. However, both IL-8 and RANTES inhibited MCP-1 and HRF-induced histamine release from basophils dose-dependently at concentrations of 10(-9) to 10(-7) M. Basophils from all donors showed a significant inhibitory response (greater than 15%). The maximal inhibition of MCP-1 and HRF by IL-8 was 28 +/- 4% and 48 +/- 8%, respectively. The maximal inhibition of MCP-1 and HRF by RANTES was 26 +/- 4% and 43 +/- 6%, respectively. Peripheral blood mononuclear cell-derived HRF was purified into three distinct peaks by reverse-phase high performance liquid chromatography. Peak I contained MCP-1 as judged by binding to an immunoaffinity column that was prepared with anti-MCP-1 antibody. IL-8 inhibited histamine release induced with all three peaks of HRF. The inhibition of histamine release by IL-8 was significantly higher in normal subjects than in allergic patients (59 +/- 9% versus 31 +/- 7%, P less than 0.05). Both IL-8 and RANTES inhibited cytokine-induced histamine release only and did not affect histamine release by anti-IgE, FMLP, and C5a.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Infective Agents; Basophils; Biomarkers, Tumor; Cell Separation; Chemokine CCL2; Chemokine CCL5; Chemotactic Factors; Chromatography, High Pressure Liquid; Histamine Release; Humans; Hypersensitivity; In Vitro Techniques; Interleukin-8; Leukocytes; Lymphokines; N-Formylmethionine Leucyl-Phenylalanine; Recombinant Proteins; Reference Values; Tumor Protein, Translationally-Controlled 1

Basophils from five of six human donors released histamine in response to neutrophil attractant/activation protein-1 (NAP-1). Histamine release by this protein was concentration-dependent over the range of 3 x 10(-7) M to 4 x 10(-6) M. At 4 x 10(-6) M, the mean agonist-induced release was 16 +/- 3% (SEM) of total basophil histamine. For the same basophil preparations, release by anti-IgE was 35 +/- 6%. The chemotactic protein did not cause release of histamine from basophils at 0 degrees C or in the presence of 10 mM EDTA. The time-course of histamine release was rapid; release was 43% of maximal after 30 s and maximal after 1 min of incubation. Thus, in addition to its previously characterized neutrophil chemotactic and activating properties, this protein activates human basophils.

Topics: Basophils; Cations, Divalent; Chemotactic Factors; Histamine Release; Humans; Hypersensitivity; Interleukin-8; Leukocytes, Mononuclear; Stimulation, Chemical; Temperature