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Biomedical subjects

D Proud

Publications and source records attributed to D Proud.

At least 91 records · Page 5Linked to original sources
PubMed1992

Production of granulocyte-macrophage colony-stimulating factor by cultured human tracheal epithelial cells.

We have evaluated the capacity of cultured human respiratory epithelial cells (HTE) to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) and have examined the ability of proinflammatory stimuli and of glucocorticoids to modulate the production of GM-CSF by these cells. Conditioned medium (CM) was obtained after 24-hr culture of HTE in the presence or absence of serum (5%) and was assayed for GM-CSF activity using the M-07e cell line, which proliferates in response to GM-CSF and interleukin-3 (IL-3). HTE produced 1.1 +/- 0.7 and 2.1 +/- 1.5 ng GM-CSF/10(6) cells in the presence or absence of serum, respectively (n = 4). The identity of this activity as GM-CSF was established by neutralization with specific antibody to GM-CSF, while antibody to IL-3 was without effect. Dexamethasone (10(-6) M) inhibited basal GM-CSF release to below the limit of detection of the assay (0.12 ng GM-CSF/ml conditioned media). GM-CSF release was significantly enhanced by 10(-6) M histamine (1.6 +/- 0.7 versus 2.13 +/- 0.8 ng GM-CSF/10(6) cells; n = 9) and 5 ng/ml interleukin-1 (IL-1) (0.6 +/- 0.2 versus 3.2 +/- 0.5 ng GM-CSF/10(6) cells; n = 3). Stimulation of GM-CSF release by IL-1 was dose-dependent. A significant increase in GM-CSF activity was observed with 0.1 ng/ml, while maximal stimulation occurred at 5 ng/ml IL-1. In kinetic studies, GM-CSF activity was first detected in CM from cells incubated in the absence of stimulus at 8 hr of incubation, and continued to increase up to 24 hr. IL-1 stimulated GM-CSF activity was detected in CM as early as 4 hr and continued to increase significantly up to 24 hr. Thus, human tracheal epithelial cells release GM-CSF and this release is regulated by inflammatory mediators and glucocorticoids.

Adult↗
PubMed1991

Interaction of platelet-activating factor with cultured guinea pig tracheal epithelial cells.

The present study has examined the interaction of platelet-activating factor (PAF) with cultured guinea pig tracheal epithelial cells (GTE). PAF stimulated GTE to release endogenous arachidonic acid and metabolize it to prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Prostanoid production by GTE in response to PAF was dose-dependent (0.1-100 nM) and was maximal within 5 min. PGE2 and PGF2 alpha levels increased by 3.3 +/- 0.8 and 3.2 +/- 0.6 ng/10(6) cells respectively over basal levels in response to 100 nM-PAF. The ability of GTE to synthesize and/or catabolize PAF was also examined. GTE readily incorporated [3H]acetate into a product which migrated on t.l.c. with PAF. However, further characterization of this product suggested that label had not been incorporated into PAF, but rather that it was incorporated into another lipid product with chromatographic characteristics similar to those of PAF. In contrast, GTE readily metabolized PAF to inactive products. When [3H]PAF was incubated with GTE, 50% of the total [3H]PAF added was catabolized in approx. 15 min. The major route of catabolism of PAF by GTE was the deacetylation-reacylation pathway, which yielded 1-O-[3H]alkyl-2-acyl-sn-glycerophosphocholine. Determination of the nature of the long-chain acyl group incorporated into the sn-2 position of the newly synthesized products revealed that oleic and linoleic acids were the major fatty acids present. Taken together, these results suggest that respiratory epithelial cells respond to stimulation by PAF with enhanced production of PGE2 and PGF2 alpha, and also have the capacity to modulate inflammatory reactions in the airways by their ability to degrade this potent inflammatory mediator.

Animals↗
PubMed1991

Mechanisms of mediator release from human skin mast cells upon stimulation by the bradykinin analog, [DArg0-Hyp3-DPhe7]bradykinin.

We have used the bradykinin analog, [DArg0-Hyp3-DPhe7]-bradykinin, as a model stimulus with which to examine peptide-induced mediator release from human skin mast cells (SMC) and to compare it with IgE-mediated release from the same cells. The bradykinin analog was an effective histamine secretagogue, inducing a comparable maximal level of release to that observed for anti-IgE. By contrast to anti-IgE, however, [DArg0-Hyp3-DPhe7]-bradykinin did not stimulate marked release of prostaglandin D2 (PGD2) from these cells. In experiments where cells were exposed to both stimuli simultaneously, histamine release was additive, while PGD2 release was the same as that observed for anti-IgE alone. The kinetics of [DArg0-Hyp3-DPhe7]-bradykinin-stimulated histamine release were rapid, with 50% of maximal release being achieved within 30 sec, compared to 2-3 min for anti-IgE. Interestingly, when both stimuli were applied simultaneously, the kinetics of release were intermediate between those of either stimulus alone. Studies of the signal transduction pathways that may be involved in [DArg0-Hyp3-DPhe7]-bradykinin-induced histamine release revealed striking differences to results obtained with anti-IgE. While agents that increase intracellular cyclic AMP have a pronounced inhibitory effect on IgE-mediated release, forskolin, isobutylmethylxanthine and isoproterenol were all totally ineffective at inhibiting histamine release induced by the bradykinin analog. Similarly, staurosporine, a relatively selective inhibitor of protein kinase C, and the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) an activator of this enzyme, both have pronounced effects on IgE-mediated histamine release from SMC but were completely inactive with regard to [DArg0-Hyp3-DPhe7]-bradykinin-stimulated release. SMC stimulated with this peptide showed characteristic changes in intracellular free calcium levels, as assessed by digital video microscopy. This response differs from that induced by anti-IgE in that it had a more rapd onset, achieved a lower peak, and decayed much more rapidly. Analysis at the single cell level showed that cells that responded in this fashion upon exposure to the bradykinin analog were capable of showing an additional response upon subsequent exposure to anti-IgE. We conclude that histamine release from SMC in response to [DArg0-Hyp3-DPhe7]-bradykinin occurs via a completely different mechanism from that in response to IgE-mediated stimuli. Peptide-induced release is rapid and is not susceptible to pharmacologic manipulation of intracellular cyclic AMP or protein kinase C but utilizes a rapid transient shift in intracellular calcium concentrations as part of its signal transduction pathway.

Antibodies, Anti-Idiotypic↗
PubMed1991

Effects of immunotherapy on the early, late, and rechallenge nasal reaction to provocation with allergen: changes in inflammatory mediators and cells.

We investigated the effects of immunotherapy (IT) on the early (ER), late (LPR), and rechallenge reactions (RCRs) to nasal challenge with antigen as well as on the cutaneous ER and LPR to intradermal skin challenge. Our expectation was that IT would have a preferential effect on the LPR, and our aim was to understand the mechanism. Twenty-one ragweed hay fever-sensitive subjects were treated with a moderate dose of antigen extract (maintenance dose of 1.94 micrograms of antigen E (Amb a I)) during a period of 8 months (total dose equivalent to 24 micrograms of antigen E), and 20 matched subjects received placebo injections in a double-blind manner. Both groups underwent identical nasal challenges and intradermal skin tests with ragweed-antigen extract both before (1985) and during (1986) IT. Symptom and medication diaries, recorded during seasonal exposure, and changes in specific serum IgE and IgG antibodies confirmed the efficacy of the administered IT dose. Between-group analysis revealed that IT significantly reduced the levels of histamine, TAME-esterase activity, and kinins, as well as symptoms of rhinorrhea and congestion generated during the ER to nasal challenge. Within-group paired analysis demonstrated ER, LPR, and RCR mediators and symptoms also to be reduced by IT. Surprisingly, the placebo-treated group demonstrated an increase in the ER. There was no decrease of the LPR without an antecedent decrease of the ER. IT did not clearly change the late cellular inflammatory response. In the case of skin challenge, IT significantly reduced the cutaneous ER. The reduction of the cutaneous LPR was more pronounced. We speculate that moderate-dose IT ameliorates seasonal symptoms of allergic rhinitis by reducing the ER, LPR, and RCR to antigen challenge but does not preferentially reduce the nasal LPR.

Allergens↗
PubMed1991

Immunotherapy decreases antigen-induced eosinophil cell migration into the nasal cavity.

We investigated the effect of immunotherapy (IT) on eosinophil (EOS) migration into the nasal cavity after nasal provocation with ragweed antigen and during seasonal exposure. In the first study, three groups of subjects participated: one group with no treatment (N = 19), one group with 10 months of IT, reaching maintenance at 2 micrograms of Amb a I (antigen E) (N = 15), and one group with 22 months of IT, reaching maintenance at 24 micrograms of Amb a I (N = 10). The percent of EOSs in nasal lavages performed during December before and 24 hours after nasal challenge with ragweed extract was determined. No significant difference between groups existed before challenge. The no treatment group demonstrated a significant increase in the percent of EOSs from 26% to 69.5% (p less than 0.008), whereas the treated groups demonstrated no significant change. In the second study, 45 patients were divided into four groups based on maintenance dose in micrograms of Amb a I and duration of treatment: (1) no treatment (N = 15), (2) 1 year at 2 micrograms (N = 13), (3) 2 years at 2 micrograms (N = 11), and (4) 3 years at 24 micrograms (N = 9). Nasal mucosal brushings were done during the ragweed season. A significantly smaller percentage of EOSs in 3-year IT-treated individuals was obtained compared to the control group (18 versus 8.4; p less than 0.04). The smaller dose of IT, regardless of duration, did not reveal a reduction compared to that in the no-treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗
PubMed1991

A competitive kinin receptor antagonist, [DArg0, Hyp3, DPhe7]-bradykinin, does not affect the response to nasal provocation with bradykinin.

1. In two double-blind, placebo controlled studies, we tested the effects of intranasal administration of 500 micrograms of a competitive kinin receptor antagonist, [DArg0, Hyp3, DPhe7]-bradykinin (NPC 567), on the response to nasal provocation with 20 micrograms of bradykinin. Nasal lavage was performed before and after provocation, and subjects recorded symptom scores. Lavages were assayed for albumin and TAME-esterase activity (indicators of vascular permeability). 2. In our initial study, 12 subjects received NPC 567 or placebo 5 min before bradykinin. After placebo, bradykinin challenge resulted in values (mean +/- s.e. mean) for albumin, TAME-esterase activity and total symptom scores of 275 +/- 51 micrograms ml-1, 32.1 +/- 7.2 counts min-1 x 10(-3), and 1.8 +/- 0.5, respectively. After NPC 567, bradykinin challenge resulted in values of 317 +/- 99 micrograms ml-1, 31.4 +/- 6.9 counts min-1 x 10(-3), and 2.6 +/- 0.4 for these parameters. No significant difference was observed between placebo and drug treatment for any parameter. 3. To evaluate if the lack of drug effect was due to its enzymatic degradation prior to bradykinin administration, a second study was performed in which NPC 567 was coadministered with bradykinin (n = 8). After placebo-bradykinin challenge, values of 168 +/- 42 micrograms ml-1, 11.3 +/- 4.0 counts min-1 x 10(-3), and 2.8 +/- 0.6 were recorded for albumin, TAME-esterase activity, and symptom scores, respectively, while following NPC 567-bradykinin challenge, these values were 174 +/- 51 micrograms ml-1, 12.3 +/- 4.1 counts min-1 x 10(-3), and 3.1 +/- 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1991

Histamine stimulation of the nasal mucosa does not induce prostaglandin or leukotriene generation or induce methacholine hyperresponsiveness.

To further define the role of histamine in the nasal mucosa, we studied the possible effect of histamine provocation on the generation of prostanoids and leukotrienes, and on the induction of hyperresponsiveness to methacholine. In separate experiments, we performed nasal challenges with histamine and measured by gas chromatography negative ion mass spectrometry and by radioimmunoassay after high-performance liquid chromatography the levels of prostanoids and leukotrienes, respectively, in recovered nasal lavages 10 min after challenge. Hyperresponsiveness to methacholine was tested in both nostrils 24 h after unilateral provocation with histamine. Our data suggest that histamine induced an immediate symptomatic response, but neither led to the generation of prostaglandins or leukotrienes nor induced hyperresponsiveness to methacholine. These results differ from those achieved after antigen stimulation and emphasize the importance of mediators in addition to histamine in the allergic reaction.

Chromatography, Gas↗
PubMed1991

Pharmacology of nasal provocation with bradykinin: studies of tachyphylaxis, cyclooxygenase inhibition, alpha-adrenergic stimulation, and receptor subtype.

We have evaluated mechanisms by which nasal provocation with bradykinin may induce symptoms of rhinitis. Repeated nasal challenges with 100 micrograms of bradykinin led to reproducible increases in symptoms and in vascular permeability. Premedication with aspirin did not alter bradykinin-induced responses. Topical application of the alpha-adrenergic agonist oxymetazoline significantly reduced bradykinin-induced subjective nasal congestion scores, but did not lead to a significant decrease in total symptoms or in vascular permeability. Finally, the B1 kinin receptor agonist des-Arg9-bradykinin (1 mg) was totally ineffective in inducing symptoms or increasing vascular permeability. Thus, nasal provocation with bradykinin leads to induction of symptoms and increased vascular permeability, presumably via stimulation of B2 kinin receptors, and is not dependent on prostanoid generation.

Aspirin↗
PubMed1991

Steroid-induced reduction of histamine release does not alter the clinical nasal response to cold, dry air.

In some persons, cold, dry air (CDA) provokes symptoms of rhinitis that are associated with increased levels of histamine and other inflammatory mediators in nasal lavages. Because the patterns of mediators released during the early reaction to antigen and CDA-induced rhinitis are similar, we believe that mast cell activation is part of the reaction to CDA. In view of our previous finding that 1-wk pretreatment with topical steroids reduced symptoms and mediator release in the early nasal response to antigen of allergic subjects, we examined the effect of beclomethasone dipropionate on the response to CDA. Using a double-blind, crossover design, 84 micrograms of beclomethasone or placebo were administered in each nostril twice a day to 13 volunteers for 7 days prior to CDA challenge. The reaction to CDA was monitored by measuring the levels of histamine, N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity and albumin in nasal lavages before and after provocation. Overall symptom scores, as well as scores for rhinorrhea and congestion, were also obtained. Cold, dry air challenge resulted in elevation over baseline of all parameters after placebo pretreatment. After beclomethasone, a significant reduction in histamine levels, but not in TAME-esterase activity or albumin levels or in number of symptoms, was observed. These results indicate that 1-wk pretreatment with beclomethasone affects mast cells, reducing histamine release after CDA, as it did in antigen-induced rhinitis. They also indicate that histamine may not be essential for the development of the immediate nasal reaction to CDA.

Adult↗
PubMed1991

Upper respiratory tract environmental tobacco smoke sensitivity.

Some patients report rhinitis symptoms after exposure to environmental tobacco smoke (ETS), but objective assessments of this response have been lacking. Furthermore, the mechanism of this response is unknown. We assessed the frequency of ETS-related symptoms by administering a questionnaire to 77 healthy nonsmoking young adults who were participating in an unrelated study. Of the subjects 34% (26 of 77) reported one or more rhinitis symptoms (congestion, rhinorrhea, or sneezing) following ETS exposure. We then exposed 10 historically ETS-sensitive (ETS-S) and 11 historically ETS-nonsensitive (ETS-NS) subjects to 15 min of clean air followed by 15 min of sidestream tobacco smoke (CO concentration of 45 parts per million). At selected time points during these procedures we recorded symptoms, posterior nasal resistance, and spirometry and performed nasal lavages. ETS-S but not ETS-NS subjects reported significant (p less than 0.01) increases in nasal congestion, headache, chest discomfort or tightness, and cough following exposure to sidestream tobacco smoke. Rhinorrhea symptoms were greater and more prolonged in ETS-S subjects compared to ETS-NS subjects. Significant (p less than 0.01) increases in perception of odor and in eye, nose, and throat irritation occurred in both study groups, but ETS-S subjects reported significantly more nose and throat irritation. No significant changes in posterior nasal resistance occurred in the ETS-NS group but a significant increase occurred in the ETS-S subjects, with the resistance rising from 3.8 +/- 0.5 cm H2O/L/s (mean +/- SE) preexposure to a peak of 8.0 +/- 2.7 cm H2O/L/s 20 min after completion of the smoke exposure (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics. Cellular, mediator, and permeability changes.

Asthma may represent the clinical manifestations of a unique form of chronic airway inflammation and is often associated with allergy. To better define the components of allergic inflammation in the lung, fluids obtained by bronchoalveolar lavage (BAL) were examined for cells, inflammatory mediators, and markers of airway permeability 5 min and 19 h following instillation of ragweed antigen directly into an airway segment of allergic asthmatic subjects. The 5-min response to antigen challenge (n = 10) was characterized by 17- to 208-fold increases in histamine, prostaglandin D2 (PGD2), and its metabolite, 9 alpha,11 beta-PGF2, thromboxane B2, and 6-keto-PGF1 alpha compared with a saline-challenged segment (0.004 less than p less than 0.017). The increases in most of these mediators were significantly correlated with each other (0.0001 less than p less than or equal to 0.01), and the magnitude of all significant mediator increases was directly correlated with skin test sensitivity to ragweed antigen (0.007 less than or equal to p less than or equal to 0.05). There was also a slight increase in kinins (p = 0.04). Changes in cells and airway permeability were not detected. In contrast, the 19-h response to antigen challenge (n = 9) was characterized by a 13-fold increase in total cells recovered by BAL. Eosinophils, basophils, and lymphocytes were significantly increased and comprised 38, 1, and 9% of total cells, respectively. A neutrophil influx was also observed but was not specific for antigen challenge since a similar change was observed in a sham, saline-challenged site.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Antigen-provoked increase in histamine reactivity. Observations on mechanisms.

To investigate the effect of antigen provocation on nonspecific reactivity to histamine, nine allergic individuals underwent multiple nasal challenges with histamine, or antigen. The response to challenge was assessed by counting the number of sneezes and measuring the levels of albumin and TAME-esterase (TAME; [3H]N-alpha-tosyl-L-arginine methyl ester) activity in recovered nasal lavages. In the case of antigen, levels of histamine were also measured. In response to histamine, the subjects sneezed and had increased levels of albumin and TAME. The responses to antigen or histamine were unchanged 24 h after histamine provocation. The responses to histamine provocations were increased with respect to symptom scores and to the levels of TAME activity and albumin in nasal lavages compared to baseline challenge, however, 24 h after antigen provocation. Increasing antigen exposure from 1 to 3 days did not further increase the responsiveness to histamine. Histamine reactivity returned to baseline 12 days after antigen exposure. The number of eosinophils, neutrophils, and alcian blue-positive cells in the lavages after antigen challenge and before the histamine challenges correlated with the changes in response to histamine. The increase in sneezing induced by antigen stimulation correlated with the increase in the same parameter after histamine provocation 24 hr after antigen challenge (r = 0.88; p less than 0.01). Surprisingly, the other parameters assessed did not show similar correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Effect of intranasal capsaicin on symptoms and mediator release.

Differential nasal responsiveness to environmental tobacco smoke (ETS) has been documented in humans and we hypothesized that this reflects differential responsiveness to c-fiber stimulation. We compared the response to intranasal capsaicin in subjects with and without a history of ETS-rhinitis. We challenged 10 ETS-sensitive and 11 ETS-nonsensitive subjects intranasally with 25 mg of lactose powder followed by 25 pg to 25 ng of capsaicin in 25 mg of lactose. Subjects rated nasal symptoms and underwent nasal lavage. In each lavage, the concentrations of albumin (an index of vascular permeability), kinins and histamine (a marker of mast cell activation) were measured. Nasal lavage tosyl-L-arginine methyl ester (TAME)-esterase activity, which can be a reflection of mast cell activation, increased vascular permeability or glandular secretion, was also determined. Subjects with a history of ETS-rhinitis reported more rhinorrhea than subjects without a history of ETS-rhinitis (P less than .01). No significant increase occurred in nasal lavage histamine, albumin or kinins in either subject group. TAME-esterase activity (presumably a reflection of increased glandular secretion) increased greater than 1000 cpm in 12/21 subjects (designated "TAME-producers"), but this was unrelated to ETS-sensitivity. TAME producers showed a dose-dependent increase in TAME-esterase activity, whereas TAME nonproducers showed no change at any capsaicin dose. We conclude that capsaicin causes nasal symptoms and glandular stimulation without evidence of increased vascular permeability or mast cell activation. ETS-rhinorrhea symptoms in humans appear related to c-fiber stimulation. The absence of c-fiber-induced glandular secretion, although not related to ETS-sensitivity, was associated with decreased sneezing and increased symptoms of capsaicin-induced nasal burning.

Administration, Intranasal↗
PubMed1990

Localized antigen challenge of the nasal mucosa.

We describe a localized nasal antigen challenge and the measurement of mediators found at the same site. Eight ragweed-allergic subjects were challenged on 2 days, 1 week apart. Challenges consisted of six sequential provocations, beginning with two control challenges (diluent for antigen-phenol-buffered saline) followed by four increasing antigen doses (0.6, 6, 60, and 160 protein nitrogen units) (antigen day) or an additional four control challenges (control day). The number of sneezes and the symptom scores increased significantly with increasing antigen doses. The levels of histamine and N-alpha-tosyl-L-arginine methyl ester-esterase activity increased in the eluted secretions on the antigen day, but not on the control day. The amount of secretions collected also increased per unit of time on the antigen day. We found no significant increase in the concentration level of either histamine or N-alpha-tosyl-L-arginine methyl ester-esterase in nasal secretions on either day. We conclude that the total amount of histamine and N-alpha-tosyl-L-arginine methyl ester-esterase activity increased per unit of time while their concentration did not.

Adolescent↗
PubMed1990

Inflammatory mediator release on conjunctival provocation of allergic subjects with allergen.

To evaluate the role of inflammatory mediators in the pathogenesis of the ocular allergic response, 23 subjects with positive histories of allergies to either cat dander or ragweed pollen and positive skin tests to the appropriate allergen extract were recruited and were subjected to conjunctival provocation. The tear duct of the left eye of each subject was blocked with a collagen plug while the right eye was left unplugged. In all cases, the eye was initially provoked with saline and subsequently with the appropriate allergen extract. Nonallergic subjects, or allergic subjects provoked with nonrelevant allergen, were used as control subjects. After each provocation, symptoms were recorded, and tears were collected with preweighed strips of filter paper (Schirmer strip). Each strip was placed into a tared tube containing fluid appropriate for the optimal preservation of the mediator to be measured. It was therefore possible to calculate the weight of tears collected and to express mediator levels per milliliter of tears. All allergic subjects demonstrated a positive symptomatic response to allergen challenge, whereas the control subjects remained asymptomatic. Blockage of the tear duct did not significantly alter the response. For allergic subjects, the levels of histamine, kinins, prostaglandin D2, albumin, and TAME-esterase activity were all significantly (p less than 0.005 in each case) greater after allergen challenge than after saline challenge. Furthermore, levels of each of these mediators after allergen challenge (expressed as increases above levels after saline provocation) were significantly greater for allergic subjects than for control subjects (p less than 0.005 in each case). Thus, the clinical response to conjunctival provocation with allergen is associated with increases in the levels of inflammatory mediators in tears.

Adolescent↗
PubMed1990

Relationship between the early, late, and rechallenge reaction to nasal challenge with antigen: observations on the role of inflammatory mediators and cells.

We challenge each of 55 consecutive ragweed (RW)-allergic patients with hay fever and with graded increasing doses of ragweed extract to investigate the frequency and relationship between the early (ER), late (LPR), and rechallenge reactions (RCRs) to nasal challenge. We evaluated the nasal response by measuring the levels of histamine, TAME-esterase activity, and kinins in the nasal lavage fluid and by grading symptoms. Fifty-one subjects (92.7%) had an ER consisting of a dose-dependent, concommitant increase in both mediators and symptoms. The total amount of TAME-esterase activity and kinins generated during ER correlated significantly with specific serum IgE (ssIgE), intradermal skin test (ST) sensitivity, and basophil histamine release (BHR) to antigen E (p less than 0.01 for each). Twenty-four (47%) subjects developed a late increase in mediators and 23 (45%) subjects in symptoms. None of the four subjects without an ER developed an LPR. The levels of the late-appearing mediators were not predicted by ST, ssIgE, or BHR. There was a significant but weak association between the intensity of ER and LPR, but there was no significant difference in the IgE antibodies, ST, BHR, and intensity or threshold of ER between dual and early only reactors. The number of eosinophils and neutrophils in the LPR lavages increased over the prechallenge baseline, and their numbers correlated (p less than 0.05) with ER kinins (r = 0.46, and 0.37, respectively), ER TAME-esterase activity (r = 0.28 and 0.24, respectively), and in the case of eosinophils, ER histamine (r = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Kinins are generated in nasal secretions during natural rhinovirus colds.

A prospective study compared the levels of inflammatory mediators in nasal lavages from noninfected, asymptomatic subjects with the mediator content of lavages from the same subjects during naturally occurring rhinovirus colds. Samples were obtained from 16 subjects who experienced natural colds that could be attributed to rhinovirus infections. Kinin levels during symptomatic colds were significantly elevated (P less than .01) compared with those measured when the subjects were noninfected and asymptomatic. Increases in kinins correlated with increased vascular permeability, as monitored by increased concentrations of albumin in lavages. In contrast, histamine levels in nasal lavages were not increased during symptomatic infections, suggesting that mast cell and basophil activation does not occur during rhinovirus colds. These data confirm and extend observations made during experimentally induced rhinovirus infections to the natural disease and are consistent with the hypothesis that kinins may play a role in the pathogenesis of symptomatic rhinovirus infections.

Adult↗