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Biomedical subjects

S Ahlstedt

Publications and source records attributed to S Ahlstedt.

At least 55 records · Page 3Linked to original sources
PubMed1994

Asthma in children less than 5 years of age: eosinophils and serum levels of the eosinophil proteins ECP and EPX in relation to atopy and symptoms.

Children less than 5 years of age with asthma were assessed for total eosinophil counts and serum levels of the eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), to determine whether these measurements would reflect eosinophilic inflammation in the airways. Initially 27 symptomatic patients, 14 atopic and 13 nonatopic were investigated. They had a mean age of 1.8 years and had never been treated with inhaled steroid and had not received Intal for 2 weeks prior to the assessment. The 14 atopic patients proved to have higher mean total eosinophil counts and serum levels of ECP and EPX than the 13 non-atopic patients (eosinophil counts 0.63 x 10(9)/l vs 0.26 x 10(9)/l, P < 0.001; ECP 36.9 micrograms/l vs 10.8 micrograms/l, P < 0.001; EPX 69.0 micrograms/l vs 19.6 micrograms/l, P < 0.01). Thirteen of these patients required treatment with daily doses of inhaled steroid and 11 had a repeat assessment (seven atopic and four non-atopic). The mean serum ECP of the seven atopic patients had fallen significantly (40.6 to 22.9, P < 0.05) while the total eosinophil counts did not. These results suggest a difference in numbers and activity of eosinophils in atopic compared with non-atopic asthma in young children. To determine whether the results were influenced by treatment with inhaled steroids, 31 patients who were being treated with daily inhaled steroid underwent assessment when they were symptomatic (22 samples) or asymptomatic (19 samples). Of the 31 patients, 11 were atopic and 20 non-atopic.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Peripheral blood eosinophil counts and eosinophil cationic protein content of respiratory secretions in bronchiolitis: relationship to severity of disease.

Infants and young children with acute viral respiratory illness were studied to determine the association of peripheral blood eosinophil counts and concentrations of eosinophil cationic protein (ECP) in nasopharyngeal secretions with the development and severity of bronchiolitis. Subjects included those with upper respiratory illness (URI) alone, pneumonia or bronchiolitis. Controls consisted of healthy infants, and those hospitalized with non-respiratory illnesses. While peripheral blood eosinophil counts were suppressed in all infected infants greater than two months of age, eosinophil counts in patients with bronchiolitis were significantly greater than in those with URI alone. ECP concentrations were significantly greater among individuals with bronchiolitis than other infected infants. For bronchiolitis cases with detectable peripheral blood eosinophils, eosinophil counts correlated weakly and inversely with oxygen saturations. In contrast, ECP concentrations were strongly inversely correlated with initial oxygen saturation. ECP concentrations were also significantly correlated with peripheral blood eosinophil counts. Viral infections suppress peripheral blood eosinophil counts in infants greater than two months of age, although the effect is somewhat overcome in patients with bronchiolitis. The form and severity of bronchiolitis is much more strongly related to degranulation of eosinophils in the respiratory tract than to peripheral blood eosinophil counts.

Blood Proteins↗
PubMed1994

Immune response against ovalbumin in rats colonized with an ovalbumin-producing Escherichia coli and the influence of feeding ovalbumin.

The influence of feeding ovalbumin (OA) on the development of IgE/IgG antibodies and delayed-type hypersensitivity (DTH) against OA was studied in rats colonized from birth with an Escherichia coli genetically manipulated to produce OA. At 21 days of age, colonized pups and pups with a normal intestinal flora were weaned onto either an OA-containing or a conventional diet without OA. At 2 months of age the colonized rats showed an increased DTH reaction to OA, but they did not have any anti-OA antibodies in serum. The rats were then immunized intracutaneously with OA in Freund's complete adjuvant. After immunization the colonized rats fed the conventional diet had a significantly higher DTH reaction to OA and significantly higher serum levels of IgE anti-OA antibodies than the uncolonized rats on the same diet. The colonized rats eating the OA-containing diet showed a 73% decrease in the DTH reaction to OA and also significantly lower levels of IgE and IgG antibodies against OA compared with the colonized rats fed conventional diet. The dams colonized as adults by the OA-producing E. coli developed IgE anti-lipopolysaccharide antibodies in serum while the pups colonized via the dams at birth did not. Neonatal colonization with an E. coli strain producing OA resulted in increased DTH reactivity against OA and priming for secondary IgE anti-OA response. Feeding the animals an OA-containing diet from weaning abrogated this intestinally induced hypersensitivity and rendered the animals orally tolerant to OA.

Animals↗
PubMed1994

TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell line KU812.

The basophilic leukaemia cell line KU812 can be induced to differentiate into basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line. KU812 cells express affinity receptors for IgE, produce histamine and tryptase and have the capacity for IgE-mediated histamine release. In this study we have examined the cytokines, produced by the Mo cell line, which are responsible for the observed differentiation-inducing effect in the KU812 cell line. It was shown that interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced differentiation in the KU812 cells and that these cytokines were responsible for the differentiation-inducing effect of the Mo supernatant. Other cytokines tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and IL-6 after 3 days cultivation with conditioned media from the Mo T-cell line. Untreated cells showed no detectable levels of TNF-alpha or IL-6 receptors indicating induction of these receptors during differentiation. Spontaneous differentiation was shown to occur under serum-free conditions which may be the result of endogenous IL-6 production through an autocrine loop. The activity of TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to the respective cytokine.

Basophils↗
PubMed1993

Intestinal reactivity in allergic and nonallergic patients: an approach to determine the complexity of the mucosal reaction.

BACKGROUND: To determine whether inflammatory markers and mediators were released in response to different intestinal antigens, studies were performed in atopic patients allergic to birch, patients allergic to psyllium powder (ispaghula), and patients intolerant to milk. METHODS: Allergy to birch and psyllium powder was documented by the presence of circulating IgE antibodies and positive skin tests. Patients intolerant to milk had negative outcomes of radioallergosorbent tests and skin tests but positive results of double-blind, placebo-controlled tests. Challenge of the intestine with different antigens was achieved by perfusion of a jejunal segment occluded between balloons. Basal and antigen-activated release of mast cell/basophil and eosinophil products and of substances emanating from the plasma and interstitial fluid was compared in perfusate fluid from patients (n = 8) and matched healthy controls (n = 8). RESULTS: Perfusate levels of albumin and hyaluronan (previous name hyaluronic acid) were increased threefold to fivefold by antigen in all patients, but not in controls. Eosinophilic cationic protein increased in patients but also in ispaghula controls. Histamine was released in response to milk, but not in patients allergic to birch or ispaghula. Prostaglandin E2 increased in milk- and birch-sensitive patients. In response to ispaghula, however, it was released in both patients and controls. CONCLUSIONS: We conclude that subclinical intestinal challenge with antigen induces an increase in the appearance rate of albumin and hyaluronan in the intestinal lumen both in atopic patients (with target organs such as the lungs or nose and eyes) and in patients with intestinal intolerance to milk. These changes in permeation are similar to those reported from other organs such as the lung. They may reflect a common response in early phase I reactions that are either IgE-mediated or occur in response to food antigens without any obvious involvement of an IgE-mediated mechanism. Subclinical provocation with intestinal antigens should prove useful for further elucidation of mechanisms underlying intestinal mucosal reactions to exogenous stimuli.

Antigens↗
PubMed1993

Total blood eosinophils, serum eosinophil cationic protein and eosinophil protein X in childhood asthma: relation to disease status and therapy.

Blood eosinophils, and serum levels of the eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured in childhood asthma. Seventeen patients mean age 11.9 years who were symptomatic with asthma, were enrolled in a study examining the eosinophil counts and eosinophil proteins at the onset of study and after treatment in relation to changes in their baseline forced expiratory volume at 1 second (FEV1) and % predicted FEV1. The patients with symptomatic asthma were compared with 17 patients mean age 12.0 years with asymptomatic asthma maintained on daily inhaled steroid and 13 patients, mean age 12.0 years, without asthma but with urticaria who served as non-asthma controls. Patients with symptomatic asthma did not have significantly higher initial eosinophil counts compared with those with asymptomatic asthma (0.43 x 10(9)/l vs 0.26 x 10(9)/l, P = 0.09) but had higher serum ECP levels (28.9 micrograms/l vs 18.5 micrograms/l). Both asthma patient groups had significantly higher serum ECP levels (P < 0.01) than the controls (9.8 micrograms/l). After therapy consisting of increased dose of inhaled steroids and/or oral steroids, patients in the symptomatic asthma group demonstrated a significant rise in FEV1 (1.67 l/sec at Visit 1 vs 2.08 l/sec at Visit 2, P < 0.001). A similar rise was seen for % predicted FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

Neutrophil mucosal involvement is accompanied by enhanced local production of interleukin-8 in ulcerative colitis.

The concentration of myeloperoxidase, a neutrophil granule constituent, was measured in the perfusion fluid from sigmoid and rectal segments in patients with ulcerative colitis. The concentrations of myeloperoxidase were increased severalfold in the patients with ulcerative colitis compared with healthy controls pointing to an enhanced neutrophil activity. The release of myeloperoxidase correlated to an enhanced local release of the neutrophil activating peptide interleukin-8 (IL-8). Increased values of tumour necrosis factor (TNF-alpha) were also found during intestinal perfusion of the patients and correlated with those of IL-8. The results obtained are compatible with the hypothesis that local mucosal recruitment/activation of neutrophils in ulcerative colitis is mediated by an enhanced IL-8 synthesis. TNF-alpha may be one relevant factor as a stimulus to IL-8 synthesis.

Adult↗
PubMed1993

Antibody response in bronchoalveolar lavage and bile in rats after aerosol immunisation with an Escherichia coli strain producing ovalbumin.

We studied the expression of the antibody response in two parts of the mucosal immune system after exposing rats to an aerosol containing an Escherichia coli O6 strain which carries type 1 fimbriae and which is genetically manipulated to produce ovalbumin (OA). For comparison rats were immunised twice in the Peyer's patches (PP), 3 weeks apart, with the same bacteria. Bile, serum and bronchoalveolar lavage (BAL) were collected from both groups and the levels of antibodies directed against O6 lipopolysaccharide (LPS), type 1 fimbriae and OA were determined. The aerosol-exposed animals all developed higher levels of IgA anti-LPS antibodies in BAL than in bile. IgA antifimbrial antibodies were not detected in BAL despite the presence of such antibodies in the bile. Thus, the ratio BAL:bile was much higher for the anti-LPS antibodies than for the antifimbrial antibodies. This was in contrast to the PP-immunised animals which developed both IgA antifimbrial as well as anti-LPS antibodies in BAL although at a lower level than in bile and the ratios BAL:bile for the antibodies against fimbriae and LPS were similar. IgA anti-OA antibodies were present in bile from both groups but not detected in BAL in any group. IgG anti-LPS antibodies were very high in BAL and in serum in the aerosol-immunised animals, while neither IgG antifimbrial nor anti-OA antibodies were detected. The PP-immunised animals on the other hand developed IgG antibodies against both the fimbrial and the LPS antigens in serum but only against fimbriae in BAL.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1992

Induction of IgE antibodies and T-cell reactivity to ovalbumin in rats colonized with Escherichia coli genetically manipulated to produce ovalbumin.

The immune response to ovalbumin (OA) and the bacterial antigens, lipopolysaccharide (LPS) and fimbriae were studied in conventional rats colonized from birth with an Escherichia coli strain producing OA. The colonized rats had developed IgE antibodies against OA, but not against the fimbrial or the LPS antigens from the E. coli at 2 months of age. At this time all rats were primed with OA given intracutaneously in Freund's complete adjuvant. Two weeks later the colonized rats showed a 35% greater delayed-type hypersensitivity (DTH) reaction to OA, measured as ear swelling, than the controls. Thus bacteria carrying antigens resembling potential allergens might aggravate, or participate in the induction of allergic symptoms. In addition such bacteria could be efficient vaccine vectors in protection against parasites. The study illustrates the importance of the mode of antigen presentation for the subsequent immune response.

Animals↗
PubMed1991

Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma.

Bronchial inflammation is a characteristic of asthma that may be examined indirectly by bronchoalveolar lavage (BAL). Nine normal individuals were compared with 38 age-matched adults with asthma of variable severity to appreciate the importance of cell activation in the severity of asthma. The severity of asthma was appreciated by the clinical score of Aas and the pulmonary function of the patients. FEV1 ranged between 35% and 130% of predicted. The indirect activation of eosinophils (EOSs), mast cells, fibroblasts, and neutrophils was examined by the titration of eosinophil cationic protein (ECP), tryptase, hyaluronan (HA), and myeloperoxidase (MPO) by radioimmunoassay in BAL fluid (BALF) and cytology of BALF. In the adults with asthma, there was a significantly increased number of EOSs and a significantly increased level of all mediators but MPO. MPO levels were increased in seven patients only; three of these patients were previous smokers. Only ECP and HA levels were significantly correlated with the severity of asthma. These results demonstrate EOSs, mast cells, and fibroblasts are activated in asthma, whereas the involvement of neutrophils is less clear. There was a significant correlation between ECP and HA levels, suggesting a common activation of EOSs and fibroblasts.

Adult↗
PubMed1991

Effects on immune responses in rats after neuromanipulation with capsaicin.

The effect of capsaicin treatment on the immune response, assessed as antibody formation in vivo and in vitro, was studied in ovalbumin (OA)-immunized rates. Rats were treated with capsaicin at 1-2 days of life or at adult age, before or after immunization. The levels of IgA, IgE and IgG antibodies as well as immunoglobulins were measured in serum and supernatants from cultured lymph node cells, spleen cells and peripheral blood lymphocytes. Capsaicin treatment affected the antibody levels depending on the timing of capsaicin treatment in relation to immunization. Different effects of capsaicin treatment were also observed on the different immunoglobulin isotypes. One of the most striking effects by capsaicin treatment was the reduction of IgA and IgG synthesis in cultured lymphoid cells from aerosol immunized animals treated with capsaicin after immunization. In contrast, in vivo the level of total serum IgA was increased in similarly treated animals. In this study we show that capsaicin treatment, which is known to decrease the levels of neuropeptides of sensory origin, has a time-dependent effect on both antibody levels in vivo as well as the formation of immunoglobulin in vitro. Although the mechanisms responsible for this are not obvious, we conclude a link between depletion of neuropeptides in sensory nerves and the antibody synthesis.

Animals↗
PubMed1991

Antibody-dependent cell-mediated cytotoxicity to beta-lactoglobulin-coated cells with sera from children with intolerance of cow's milk protein.

The capacity of serum antibodies against beta-lactoglobulin to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) was analysed in sera from children with cow's milk protein intolerance (CMPI). The children with CMPI were divided into three groups according to clinical features: delayed-onset CMPI with gastrointestinal symptoms (n = 8); immediate-onset CMPI with gastrointestinal and skin symptoms (n = 8); and immediate-onset CMPI with skin symptoms only (n = 8). The CMPI groups were compared with children with untreated (n = 9) or treated (n = 8) coeliac disease and a control group (n = 22). Sera from the children were examined for cytotoxic effects using lymphocytes from healthy adults as effector cells and radiolabelled beta-lactoglobulin-coated erythrocytes from the same donor as target cells. In addition, IgG and IgA serum antibodies against beta-lactoglobulin were determined with ELISA. Sera from children with CMPI and gastrointestinal symptomatology showed a significantly increased capacity to induce ADCC reactivity as compared with controls. This increased capacity was seen in sera from those with immediate as well as delayed onset of the gastrointestinal symptoms. In contrast, sera from children who had an immediate-onset CMPI with only skin symptoms mediated no such increase in ADCC reactivity. Moreover, children with coeliac disease with a few exceptions, demonstrated low ADCC reactivity, despite the fact that they had high levels of antibodies against beta-lactoglobulin. ADCC may be an immunopathogenic mechanism in certain cases of CMPI with gastrointestinal symptoms.

Antibodies↗
PubMed1991

Enhancement of IgE synthesis in the human myeloma cell line U-266 with an IgE binding factor from a human T-cell line.

An IgE-binding factor(s) (IgE-BF(s] was partially purified from the supernatant of human HTLV-II carrying T-cell line MO. This IgE-BF(s) was shown to increase the IgE synthesis in the human myeloma cell line U-266, but did not affect its viability or growth. The effect of the IgE-BF(s) was dose-dependent and selective for IgE protein synthesis as beta 2-microglobulin synthesis in the U-266 and the immunoglobulin production in the U-1958 IgG-secreting human myeloma cell line were unaffected. The IgE-BF(s) increased the production of the epsilon heavy chain but not the lambda light chain production. The IgE-BF(s) was distinct from IL-1 beta, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, -beta, -gamma, M-CSF, and fragments of CD23.

Cytokines↗
PubMed1991

Local immune response and bronchial reactivity in rats after capsaicin treatment.

The interaction between the nervous system, immune system and bronchial reactivity was studied in rats by using the neurotoxin capsaicin. Rats were treated with capsaicin at 1-2 days of age or at adult age, before or after sensitization by subcutaneous injections with ovalbumin (OA). The levels of the neuropeptides neurokinin A and calcitonin gene-related peptide were decreased in the lung after capsaicin treatment, as determined with radioimmunoassay, whereas the levels of neuropeptide Y were unaffected. The levels of IgA, IgE and IgG in bronchial lavage were also affected by capsaicin treatment; however, the results were heterogeneous. Capsaicin treatment after sensitization reduced the bronchial reactivity to challenge with OA aerosol and serotonin iv. The results demonstrated that reduction of neuropeptide levels with capsaicin affected both bronchial reactivity and the levels of antibodies in bronchial lavage fluid. However, no correlation between these two parameters was seen, demonstrating the complexity of the system.

Animals↗
PubMed1991

IgE-positive duodenal mast cells in patients with food-related diarrhea.

Thirty-seven consecutive adult patients with a history of adverse reactions to foods, manifested mainly as diarrhea, were investigated with skin prick test (SPT), IgE levels in serum, and the presence of IgE bound to mast cells in duodenal biopsy specimens. Nineteen percent had increased serum IgE levels indicating the presence of atopic disease and in 35% positive SPTs for one or several allergens related to their gastrointestinal symptoms were found. In 92% of the patients with positive SPTs to food, IgE-positive mast cells in duodenal biopsy specimens were found, twice as many as in patients with negative SPTs (47%). Forty-two percent of normal individuals without any adverse reactions to foods had IgE-bearing mast cells in their intestinal mucosa. The results showed that 'arming' of mast cells with IgE locally was relatively prominent but not consistent in the gut of patients with food-related diarrhea suggested to be allergic by positive SPT. Intestinal IgE-mediated hypersensitivity reactions could be of pathogenetic significance in most of these patients. However, since also half of the normal individuals were found to have IgE-positive intestinal mast cells, this phenomenon presumably also reflects a normal physiological defence mechanism.

Adult↗
PubMed1991

Cultures of human cord blood metachromatic cells in relation to family history of atopy, development of atopic disease, nasal metachromatic cells and perinatal factors.

The appearance of basophilic cells by maturation from progenitors was studied in cultures of cord blood mononuclear cells (CB-MNC) from 83 newborns. In unstimulated cultures, the numbers of basophilic cells increased 5-fold after 14 days of cultivation. This increase and the cell numbers were similar in cultures from atopic individuals and controls. Other cultures were stimulated with conditioned medium (CM) prepared from 3-day cultures of blood cells from atopic individuals activated with allergen or with CM from the Mo leukemic cell line. The addition of such CM resulted in an increase in the number of basophilic cells, as compared to the cultures which were unstimulated (p less than 0.01). No correlation was found between the maturation of basophils and heredity for atopy, development of atopic disease, appearance of metachromatic cells in the nasal mucosa and perinatal factors, such as maternal infections, perinatal stress, birth weight, month of birth and IgE levels. The study confirmed that basophilic cells can be driven to mature in cultures of CB-MNC, although the maturation did not seem to depend on atopic predisposition as indicated by family history of allergy and CB IgE levels nor on symptoms and signs of atopic disease during the first 18 months of life. Therefore, the predictive value of elevated basophilic cell numbers in CB or CB-MNC cultures with regard to allergic disease seemed to be limited.

Basophils↗