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Biomedical subjects

K Larsson

Publications and source records attributed to K Larsson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Inhalation of swine-house dust increases the concentrations of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1ra) in peripheral blood.

Inhalation of dust in swine confinement buildings causes airway inflammation and systemic symptoms. The proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) increase in bronchoalveolar and nasal lavage fluid, and in serum. The aim of this investigation was to study changes in the IL-1 family of cytokines in peripheral blood in 36 healthy volunteers exposed to swine house dust for 3 h. Interleukin (IL-1 beta) was measured in platelet poor plasma and in a mononuclear cell fraction (PBMC) and interleukin-1 receptor antagonist (IL-Ira), IL-6 and TNF-alpha were measured in serum 4 and 7 h after the start of 3 h exposure. Lung function and a methacholine bronchial provocation test were performed before and 7 h after the start of exposure. The leukocyte count in whole blood and the mononuclear cell count in PBMC were examined before, and 4 and 7 h after the start of exposure. The concentration of airborne inhalable dust and endotoxin were measured using personal samples. The concentration of inhalable dust was 23 (20-30) mg m-3 (median 25th-75th percentile) endotoxin was 1.1 (0.8-1.4) micrograms m-3 and respirable dust (n = 8) was 1.0 (0.7-1.2) mg m-3. IL-1 beta increased from < 0.125 to 0.9 (0.5-1.3) ng l-1 in plasma and from 1.6 to 2.7 (1.1-4.4) ng l-1 in PBMC (P < 0.01). IL-1 ra, IL-6 and TNF-alpha increased 2-, 12- and 2-fold in serum after exposure, respectively. Changes in IL-1 ra correlated with changes in FEV1, bronchial responsiveness, oral temperature (P < 0.01) and blood white cell count (P < 0.05). IL-1 beta correlated significantly with temperature (P < 0.05). These results indicate that IL-1 beta and IL-1 ra increase in peripheral blood following inhalation of swine house dust and may participate in and modulate the inflammatory response together with IL-6 and TNF-alpha.

Adolescent↗
PubMed1998

Polymers that reduce intraperitoneal adhesion formation.

BACKGROUND: Viscous macromolecules and phospholipids have been shown to reduce postoperative adhesion formation. The ideal agent, or combination of agents, still remains to be identified. METHODS: The effect of hydrophobically modified ethyl (hydroxyethyl) cellulose (HM-EHEC) and polyquarternium-24 (LM-200), two cellulose-derived polymers, and of sphingomyelin, was examined in an animal model. Adhesions were induced in the parietal peritoneum in a standardized manner and quantity, and the morphology of adhesion formation was evaluated after 7 days. RESULTS: A significant reduction in adhesion formation was seen in animals receiving LM-200 (P=0.013) and HM-EHEC (P=0.012) as a short-term treatment compared with controls given saline, but not in animals receiving sphingomyelin (P=0.733). Additional effects were seen in the animals receiving LM-200 as a prolonged treatment (P< 0.001) compared with controls. There was no difference in the magnitude of the inflammatory response between the groups. CONCLUSION: These results suggest that hydrophobically modified polymers are efficient in reducing adhesions, without affecting the inflammatory response.

Animals↗
PubMed1998

Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine.

BACKGROUND: Acute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear. METHODS: Ten non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E4 (LTE4) and 9 alpha, 11 beta-PGF2, the earliest appearing urinary metabolite of prostaglandin D2 (PGD2), were measured. Bronchial responsiveness to methacholine was determined five days before and the day after the exposure. RESULTS: Methacholine PD20FEV1 decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p < 0.01). Associated with the increase in bronchial responsiveness there was a significant mean difference between post- and prechallenge levels of LTE4 (difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p < 0.01) and 9 alpha, 11 beta-PGF2 (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p < 0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fold increase in the total cell number and a 12-fold increase in IL-8 levels in the nasal lavage fluid. The levels of LTB4 and LTE4 in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively. CONCLUSIONS: The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased bronchial responsiveness following inhalation of organic swine dust.

Adult↗
PubMed1998

Induction of IL-8 production in human alveolar macrophages and human bronchial epithelial cells in vitro by swine dust.

BACKGROUND: Exposure to swine dust causes an intense airway inflammation with increased levels of interleukin 8 (IL-8) and predominantly neutrophils in the nasal and bronchoalveolar lavage fluids of healthy human subjects. It is not clear which components in the swine house environment are responsible for the airway reaction. The aim of the present study was to evaluate and compare the effect in vitro of swine dust components on human alveolar macrophages and bronchial epithelial cells. METHODS: Normal human bronchial epithelial cells (NHBE), human pulmonary epithelial carcinoma cell line (A549), and human alveolar macrophages were stimulated with swine dust, lipopolysaccharides (LPS; present in Gram negative bacteria), grain dust (swine feed components), and glucans (a structural component of fungi) in a dose response manner (1-100 micrograms/ml). RESULTS: Swine dust at a concentration of 100 micrograms/ml increased IL-8 production 20 fold in NHBE cells, 28 fold in A549 cells, and 15 fold in macrophages. LPS (100 micrograms/ml) stimulated all three cell types significantly, in macrophages to the same extent as swine dust, but in NHBE and A549 cells swine dust was 5-8 times as potent. Grain dust (100 micrograms/ml) had no effect in A549 cells and macrophages but not NHBE cells. Both glucans and grain dust were weaker stimuli than swine dust and LPS. The LPS content of swine dust solution was 2.16 (0.2) ng/100 micrograms and of grain dust was 0.53 (0.04) ng/100 micrograms. CONCLUSIONS: Swine dust is a strong stimulus for IL-8 production in both bronchial epithelial cells and human alveolar macrophages, whereas LPS has different potency in these cells.

Animals↗
PubMed1998

Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects.

Prolonged exposure to cold air may induce a chronic asthma-like condition in healthy subjects as has been demonstrated in cross-country skiers. In the present controlled study, our aim was to elucidate further the link between cold air exposure and airway inflammation by assessing the cellular influx and mediator levels within the airways following acute exposure to cold air. Bronchoalveolar (BAL) and nasal lavages were performed after exposure to cold air (-23 degrees C) and normal indoor air (+22 degrees C) during a light, intermittent work for 2 h in a cross-over design in eight healthy, nonsmoking, subjects. Analyses of inflammatory cell number, cell activation markers, pro-inflammatory cytokines, albumin and interleukin (IL)-8 in lavage fluids were performed. The number of granulocytes and of alveolar macrophages in BAL fluid was significantly higher after cold air exposure (p<0.05). No increase in BAL fluid lymphocytes and no signs of lymphocyte activation in BAL fluid were found. The concentration of IL-8 was unchanged. There were no signs of granulocyte activation (myeloperoxidase, eosinphilic cationic protein) in BAL fluid. Cold air did not influence the number of inflammatory cells or the concentration of albumin and IL-8 in nasal lavage fluid. In conclusion, exposure to cold air induces an increased number of granulocytes and macrophages in the lower airways in healthy subjects without influencing other inflammatory indices such as cellular activation, plasma leakage and pro-inflammatory cytokines. These findings support the hypothesis that cold air could be of pathogenetic importance in the asthma-like condition previously found in cross-country skiers.

Adult↗
PubMed1998

Effects of beta2-agonists and budesonide on interleukin-1beta and leukotriene B4 secretion: studies of human monocytes and alveolar macrophages.

The aims of the present study were to determine whether beta2-agonists (short- and long-acting) and a glucocorticoid (budesonide) influence the secretion of a pro-inflammatory cytokine (interleukin-1, [IL-1]) and a granulocyte attractant (leukotriene B4 [LTB4]) and to compare these effects on blood monocyte and alveolar macrophages. Alveolar macrophages (obtained by bronchoalveolar lavage) and blood monocytes from 26 healthy nonsmokers were stimulated with lipopolysaccharide or human serum opsonized zymosan. The influence of four beta2-agonists (salbutamol, terbutaline, formoterol, and salmeterol) and a corticosteroid (budesonide) on the release of interleukin-1beta (IL-1beta) and LTB4 was studied in a dose-response manner (10(-8)-10(-5) mol/L for beta2-agonists and 10(-10)-10(-6) mol/ L for budesonide). The stimulated IL-1beta secretion was significantly greater in blood monocytes than in alveolar macrophages (p < 0.05), but alveolar macrophages were much more capable of secreting LTB4 than were blood monocytes (p < 0.001). Budesonide significantly inhibited the release of IL-1beta from blood monocytes (p < 0.001), but no such effect was observed in alveolar macrophages. Budesonide did not influence the release of LTB4 in either cell type. The beta2-agonists neither influenced the LTB4 nor the IL-beta secretion in either cell type with the exception of formoterol, which stimulated IL-1beta secretion at the highest concentration (10(-5) mol/L, p < 0.05). In conclusion, beta2-agonists exhibited only minor effects on IL-1beta secretion from blood monocytes and no effect on LTB4-secretion from either cell type, and budesonide effectively inhibited the IL-1beta release in blood monocytes, but not in alveolar macrophages. Thus, induced secretion of LTB4 and IL-1beta , and the sensitivity to corticosteroids with regard to IL-1beta secretion, change during the transformation from blood monocytes to alveolar macrophages.

Administration, Topical↗
PubMed1997

Covalent binding of proteins to grafted plastic surfaces suitable for immunoassays. II. Picograms of IgE detected in BAL fluid in sarcoidosis.

An ELISA is described for the quantitation of minute amounts of human IgE using microtiter strips which were surface modified according to a procedure previously described. This ELISA used an IgG fraction of a rabbit polyclonal anti-IgE antibody coupled to the carboxylated surface, which prior to coupling had been preactivated with a water soluble carbodiimide. A biotinylated affinity purified rabbit anti-IgE antibody was used together with streptavidin conjugated alkaline phosphatase and biotinylated enzyme for the detection of bound analyte. Sarcoidosis is a systemic disorder of as yet unknown cause with epithelioid granuloma formation in the lung as a prominent feature. With the bronchoalveolar lavage technique, epithelial lining fluid was obtained and analyzed for IgE content since differences of immunoglobulin concentration in bronchoalveolar lavage fluid (BALF) may reflect disease activity. Our modified ELISA system was used for measuring IgE in BALF from healthy controls and sarcoid patients. The assay using modified strips demonstrated a considerably improved sensitivity compared to the use of physical adsorption of first antibody to untreated strips. The detection limit of the improved assay was approximately 3 pg IgE/sample (100 microl). Quantitative recovery of IgE was demonstrated within the measuring range (51.2-12500 pg IgE/ml) and more than 40% (23/54) of the sarcoid patients showed values above the lowest standard concentration (51.2 pg/ml). In contrast, none of the healthy controls (0/22) had detectable IgE as defined by the detection limit of the assay.

Adult↗
PubMed1997

[Beta-2-agonists are still of value. Tolerance does not affect the bronchodilating effect].

Use of the potent bronchodilators, beta 2-adrenoceptor agonists, has been a cornerstone of the treatment of obstructive lung disease, especially asthma, for the past 30 years. However, the occurrence of side effects and the development of tolerance have been discussed as limitations to their use. beta 2-Adrenoceptors are located on the surface of most cell types throughout the human body, and treatment with beta 2-agonists may exert effects in a wide variety of tissues. As with other pharmacological receptors, beta 2-adrenoceptors in most tissues develop tolerance as a result of continuous beta 2-stimulation. However, the bronchodilatory effect appears to be unaffected by the development of tolerance. Interestingly, most studies have yielded evidence suggesting tolerance development regarding protection against bronchoconstrictor stimuli such as methacholine, adenosine and exercise. Although the protective effect of a beta 2-agonist becomes attenuated with continuous treatment, this tolerance is partial and adequate residual protective effect remains.

Adrenergic beta-Agonists↗
PubMed1997

On periodic curvature and standing wave motions in cell membranes.

Cell membranes can form cubic arrangements and there is evidence for the occurrence of periodic curvature in simple membranes. The periodicity of the bilayer implies a standing wave character of vibrational motions. It is proposed that the periodic curvature reflects a dominating mode of standing wave oscillations, with the different cubic bilayer structures representing alternative standing wave conformations of the bilayer. The wave motions in lamellar liquid-crystalline phases, as well as in vesicles and membranes, which lack lateral periodicity, are known to exhibit statistically distributed undulations. The standing wave character of conformational fluctuations of periodically curved membranes, on the other hand, results in an organisation in time and space. Calculated models of standing wave conformations of membranes are demonstrated, and functional aspects of such biomembranes are discussed.

Cell Membrane↗
PubMed1997

Identification of framework residues in a secreted recombinant antibody fragment that control production level and localization in Escherichia coli.

The monoclonal antibody 5T4, directed against a human tumor-associated antigen, was expressed as a secreted Fab superantigen fusion protein in Escherichia coli. The product is a putative agent for immunotherapy of non-small cell lung cancer. During fermentation, most of the fusion protein leaked out from the periplasm to the growth medium at a level of approximately 40 mg/liter. This level was notably low compared with similar products containing identical CH1, CL, and superantigen moieties, and the Fv framework was therefore engineered. Using hybrid molecules, the light chain was found to limit high expression levels. Substituting five residues in VL increased the level almost 15 times, exceeding 500 mg/liter in the growth medium. Here, the substitutions Phe-10 --> Ser, Thr-45 --> Lys, Thr-77 --> Ser, and Leu-78 --> Val were most powerful. In addition, replacing four VH residues diminished cell lysis during fermentation. Thereby the product was preferentially located in the periplasm instead of the growth medium, and the total yield was more than 700 mg/liter. All engineered products retained a high affinity for the tumor-associated antigen. It is suggested that at least some of the identified framework residues generally have to be replaced to obtain high level production of recombinant Fab products in E. coli.

Amino Acid Sequence↗
PubMed1997

Postnatal testicular secretions partially restore the disturbances in reproductive activity caused by prenatal hormonal manipulation.

Male rats that prenatally had been exposed to an antiestrogen, nitromifene citrate (CI 628), showed evidence of impaired defeminization and masculinization in adulthood, suggesting a role of endogenous estrogen for the sexual differentiation of the male. The present study was undertaken to investigate a possible role of postnatal testicular secretions for the above behavioral effects. Male rats were exposed prenatally to CI 628 (1 mg/rat) or saline, and castrated on Day 0, Day 10, or Day 90 after birth. After treatment with gonadal hormones in adulthood, the males were tested for feminine and masculine sexual behavior and for sexual orientation, both when sexually naive and after they had acquired sexual experience. The following conclusions were drawn: 1. Permanent deficits of lordotic behavior were observed in all experimental groups, suggesting the importance of prenatal estrogen for the defeminization process. 2. Hop/darting and ear wiggling behaviors were enhanced in Day-0 and Day-10 castrates, and blocked in the Day-90 castrates. The restitution of these behaviors to normal levels in Day-90 castrates suggests that, in addition to prenatal estrogen, postnatal testicular secretions also are involved in the behavioral defeminization process. 3. Prenatal estrogen contributes to masculinization as evidenced by the impaired ejaculatory behavior observed in all experimental groups. 4. Male-typical sexual orientation toward the female seems to be facilitated by prenatal estrogen. Both the masculinization and the defeminization of male-typical sexual orientation toward a female were impaired by castration at birth and at Day 10 in the experimental animals, but a full restoration of the sexual orientation toward females was seen in Day-90 castrates, suggesting the restorative role of postnatal testicular secretions for these processes.

Animals↗
PubMed1997

Specific involvement of central 5-HT1A receptors in the mediation of male rat ejaculatory behavior.

The aminotetralin 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), pharmacologically characterized as a 5-HT1A receptor agonist, produces a pronounced decrease in ejaculation latency in the male rat. Stimulation of 5-HT receptors by a pharmacologically induced increase in the synaptic availability of 5-HT has been shown to produce the opposite effect. The 8-OH-DPAT-induced decrease in ejaculation latency is specific for this compound, and some chemically related ergot derivatives. In this paper we review the evidence in support for stimulation of serotonergic autoreceptors of the 5-HT1A receptor subtype as a mechanism of action for effects by 8-OH-DPAT on male rat ejaculatory behavior. We also present the questions posed by the fact that quinpirole and lisuride both produce 8-OH-DPAT-like effects on male rat ejaculatory behavior. The effects by quinpirole, lisuride of 8-OH-DPAT are not sensitive to pretreatment with the DA D2/3 receptor antagonist raeclopride. Continued studies will show whether the effects of quinpirole and lisuride can be related to stimulation of 5-HT1A receptors, of all these compounds have as yet undefined common properties.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Influence of a beta2-agonist on physical performance at low temperature in elite athletes.

Beta2-agonists are frequently used by elite cross-country skiers, a group of athletes with a high prevalence of asthma. It has been claimed that beta2-agonists have a positive effect on physical performance. The aim of the present study was to investigate whether inhalation of a beta2-agonist increases physical performance at low temperature in healthy, nonasthmatic athletes with normal bronchial responsiveness. Twenty elite male athletes (cyclists, cross-country skiers, middle and long distance runners) with no history of allergy or airway disease and who had normal spirometry and methacholine bronchial provocation tests performed a maximal exercise test on a treadmill in a climate chamber at approximately 10 degrees C on two subsequent days. Before exercise they inhaled terbutaline (3 mg from MDI) or placebo in a randomized, single blind manner. After 10-min warm-up on the treadmill, a submaximal work preceded a stepwise increase of the workload until exhaustion. Lung function, ventilation, oxygen uptake, and heart rate were determined and blood samples for lactate and potassium analyses were drawn before, during, and after exercise. Terbutaline induced a significant bronchodilatation; FEV1 increased from 4.8 (4.4-5.1) L to 5.0 (4.6-5.4) L, mean (95% CI). There were no significant differences between the two treatments with regard to exercise time, 25.1 (24.3-25.8) min vs 24.9 (24.1-25.6) min, oxygen uptake and ventilation during exercise, or heart rate at maximal workload. Terbutaline induced an increase in serum lactate concentration but did not influence the lactate response to exercise. The serum potassium increase was attenuated at low workload but not at maximal work. The postexercise decrease in serum potassium concentration was significantly greater after terbutaline (-0.52 (-0.29 to -0.76) mmol x L-1) than after placebo (-0.13 (0.06 to -0.32) mmol x L-1 (P < 0.001). We conclude that inhalation of a beta2-agonist (terbutaline) in a dose that yields significant bronchodilatation does not influence physical performance at low temperature in healthy athletes. Acute inhalation of the beta2-agonist amplified the postexercise hypokalemia, a finding of unclear significance. Although there is a slight bronchodilatation and potential negative airways effect of cold air inhalation, a beta2-agonist does not increase physical performance in top athletes.

Adolescent↗
PubMed1997

Recording non-nutritive sucking in the neonate. Description of an automatized system for analysis.

A new method for automatic analysis of non-nutritive sucking in newborn infants is described, which uses a specially designed computer program that analyses an analogue signal obtained from a pressure transducer inside a pacifier. Validation is done with four independent methods: electromyogram, visual identification, control of the automatic treatment and comparison of inter-observer results. A high degree of correspondence is shown. The system was applied to 58 healthy full-term neonates. Infants less than 24 h old demonstrated a significantly different sucking pattern compared with the 3-day-old infant. The duration of their bursts was longer (3.7 vs 2.8 s), the frequency of their sucking was lower (1.7 vs 2.0 Hz) and the variability of their sucking pattern was greater. These results also testify to the validity of the method inasmuch as the values for the different sucking parameters are similar to corresponding values presented earlier.

Age Factors↗
PubMed1997

Effect of exposure to swine dust on levels of IL-8 in airway lavage fluid.

BACKGROUND: Inhalation of swine dust causes airway inflammation with influx of inflammatory cells, predominantly neutrophils, into the lungs. A study was undertaken to determine whether or not exposure to swine dust induces release of interleukin 8 (IL-8) into upper and lower airways and how this possible release is related to cellular influx. A further aim was to study the relationship between the inflammatory response and swine dust exposure. METHODS: Thirty one healthy, non-smoking, previously unexposed subjects were exposed to swine dust during three hours work in a swine house. Bronchoalveolar lavage (BAL) was performed two weeks before and 24 hours after the exposure (n = 16). Nasal lavage and acoustic rhinometry were carried out 1-2 hours before and seven hours after the start of the exposure (n = 31). Exposure measurements were performed with personal sampling equipment. RESULTS: The exposure led to 19-fold and 70-fold increases in the neutrophil concentrations in nasal lavage and BAL fluid, respectively (p < 0.001). In BAL, fluid macrophages, lymphocytes and eosinophils increased significantly. The IL-8 levels in BAL fluid increased from < 31.3 ng/l to 63 (43-109) ng/l (median (25-75th percentile), p < 0.001), and in nasal lavage fluid the concentrations increased from 144 (97-227) ng/l to 1064 (864-1437) ng/l (p < 0.001). IL-8 levels showed a significant correlation with the increase in neutrophils in the nasal lavage fluid but not in the BAL fluid. Acoustic rhinometry demonstrated significant swelling of the nasal mucosa. The air concentration of inhalable dust was 23.3 (20.0-29.3) mg/m3, endotoxin 1.3 (1.1-1.4) micrograms/m3, and muramic acid 0.99 (0.78-2.1) microgram/m3. CONCLUSIONS: The concentration of IL-8 increases in BAL fluid and nasal lavage fluid following exposure to swine dust and may be one of the chemoattractants contributing to the recruitment of neutrophils to the nasal cavity and the alveolar space.

Adult↗
PubMed1997

Increased number of activated lymphocytes in human lung following swine dust inhalation.

Inhalation of swine dust causes intense alveolar inflammation, with recruitment of inflammatory cells, predominantly neutrophils, but also alveolar macrophages and lymphocytes. The present study focuses on the lymphocyte response to inhaled swine dust. Twenty four healthy, nonsmoking, nonallergic subjects were exposed to swine dust for 3 h in a swine confinement building. Bronchoalveolar lavage (BAL) was performed before and 24 h after the start of exposure, and blood samples were drawn before, and at 7 and 24 h after exposure. Total and differential cell counts were carried out. Monoclonal antibodies recognizing T-cells, T-cell subsets, T-cell activation markers, and B-cells were analysed by flow cytometry. The number of granulocytes increased more than 50 times and alveolar macrophages and lymphocytes increased two- to three-fold in BAL fluid. The exposure did not alter the proportion of T-cells but increased the number of activated T-cells in BAL fluid. The interleukin-2 (IL-2) receptor (CD25), human leucocyte antigen-DR (HLA-DR) major histocompatibility complex (MHC) class II and the early activation marker CD69 were expressed by 8.4% (25-75th percentiles 6.4-9.6%), 9.9% (8.2-21.6%) and 22.0% (18.1-24.3%) of the lymphocytes prior to exposure, and 11.6% (9.0-16.4%) (p < 0.01), 18.8% (12.9-30.4%) (p < 0.01) and 42.1% (38.4-47.3%) (p < 0.05), respectively, after the exposure. In peripheral blood, the concentration of T-cells decreased after exposure and B-cells increased slightly but significantly. The ratio naive/memory T-cells (CD45RA/RO) did not change in blood. In conclusion, 3 h of swine dust inhalation led to an influx of lymphocytes into the lower airways and increased expression of lymphocyte activation markers on the cell surface in previously unexposed subjects. The finding suggests a role for T-cells, in conjunction with other cells, in the inflammatory response to inhaled swine dust.

Adult↗
PubMed1997

Inhalation of swine dust induces cytokine release in the upper and lower airways.

In healthy subjects, acute inhalation of swine dust causes an influx of inflammatory cells into the airways and increased bronchial responsiveness. The exposure may also cause fever and generalized symptoms. It seems likely that proinflammatory cytokines are involved in the response to inhaled swine dust. Nasal and bronchoalveolar lavage (BAL) were performed before, and 7 and 24 h after the start of 3 h exposure to swine dust, during a period of work in a swine confinement building, in 22 healthy subjects. Lavage fluids were analysed with regard to the cellular response and concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Each subject carried personal samplers for exposure measurements. Inhalable dust and airborne endotoxin, 3-hydroxylated (2-OH) fatty acid and muramic acid were measured. Bronchial responsiveness to methacholine was investigated 1-2 weeks before and 7 h after the start of the exposure. Exposure caused fever (> 38 degrees C) in three subjects, and approximately 25% of the subjects experienced symptoms. Bronchial responsiveness to methacholine increased by 3.5 (1.6-4.8) doubling doses (median (25th-75th percentile)). Following exposure, granulocytes increased more than 50 fold in BAL fluid and more than 40 fold in nasal lavage fluid. IL-1 alpha and IL-1 beta increased significantly in BAL fluid (p < 0.05) and nasal lavage fluid (p < 0.01). IL-6 increased 25 fold in BAL and 15 fold in nasal lavage fluid (p < 0.001). TNF-alpha was below detection limit (0.25 ng.L-1) in most subjects before exposure and increased following exposure to 3.8 (2.4-5.7) and 1.3 (0.6-2.3) ng.L-1 in BAL and nasal lavage fluid, respectively, (p < 0.001). Total inhalable dust was 20.5 (14.6-30.0) mg.m-3 and the concentrations of airborne endotoxin, 3-OH fatty acid and muramic acid were 1.2 (0.8-1.4), 3.5 (2.2-4.5) and 0.9 (0.3-1.9) microgram.m-3, respectively. There was a significant correlation between the IL-6 response in BAL fluid and exposure to dust endotoxin activity and 3-OH fatty acids (p < 0.05). Otherwise, no significant correlations were found between exposure and the cytokine response. We conclude that exposure to swine dust causes an intense upper and lower airway inflammation, which involves the proinflammatory cytokines interleukin-1, interleukin-6 and tumour necrosis factor-alpha.

Adult↗