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N F Adkinson

Publications and source records attributed to N F Adkinson.

At least 127 records · Page 7Linked to original sources
PubMed1986

Characterization of inflammatory mediator release from purified human lung mast cells.

The release of inflammatory mediators (histamine, PGD2, TxB2, and LTC4) from purified human lung mast cells was characterized by kinetic and anti-IgE dose-response parameters. The relative rate of mediator release was histamine greater than PGD2 = TxB2 greater than LTC4, with one half maximal release occurring at approximately 2, 5, and 10 min, respectively. In 2 experiments, stimulation with anti-IgE caused significant quantities of platelet-activating factor (PAF) to appear rapidly (2 min) in the cell pellet; cell-associated PAF declined to low levels by 45 min. The optimal concentration of anti-IgE for the release of the arachidonate cyclooxygenase metabolites PGD2 and TxB2 (0.3 microgram/ml) was 10- to 30-fold less than that required for the release of histamine and LTC4 (3 to 10 micrograms/ml), suggesting that these release processes may have differential IgE Fc receptor cross-linking requirements. At optimal histamine release, the magnitude of the release of each arachidonate metabolite was found to correspond to the magnitude of histamine release, however, suggesting that the 2 processes are linked either in series or in parallel.

Antibodies, Anti-Idiotypic↗
PubMed1986

Local generation of sulfidopeptide leukotrienes upon nasal provocation with cold, dry air.

In order to assess whether sulfidopeptide leukotrienes are generated following nonimmunologic stimulation of inflammatory cells in vivo, 11 subjects complaining of symptoms of rhinitis when exposed to cold and dry environments were challenged by nasal breathing, first with warm, moist air and then with cold, dry air. Nasal lavages with normal saline were performed before and after each exposure. Immunoreactive leukotriene in the lavage fluids was significantly increased following cold, dry air exposure (2.6 ng/ml) compared with that after warm, moist air exposure (0.7 ng/ml) or at baseline (0.4 ng/ml) (p less than 0.01 in both instances). Six more subjects, denying cold-air sensitivity, were subjected to the same protocol and had no mediator and symptom score changes after cold, dry air challenge. Leukotriene changes after cold, dry air were highly concordant with increments in histamine, prostaglandin D2,N-alpha-tosyl-L-arginine methyl ester (TAME) esterase(s) activity and symptom scores (p less than 0.001). Separation of leukotrienes by high performance liquid chromatography in the nasal washes of 3 subjects showed variable amounts of LTC4, D4, and E4, suggesting metabolism of the former to the latter 2. To our knowledge, this is the first in vivo demonstration of leukotriene production in response to a physical stimulus, and it suggests a possible role of these and other inflammatory mediators in pathologic conditions, such as exercise-induced asthma, that involve physical causative factors.

Air↗
PubMed1986

Mediator release from human lung under conditions of reduced oxygen tension.

Although the mechanism underlying hypoxic pulmonary vasoconstriction remains undefined, various reports have suggested that mast cells and cell-derived mediators may be important in the production of this phenomenon. We investigated the effect of reducing oxygen tension on the release from human lung fragments of the mast cell-derived mediators histamine, prostaglandin (PG) D2 and peptide leukotrienes, as well as the release of the largely non-mast cell-derived mediators PGE2, PGF2 alpha, prostacyclin metabolite (6-keto-PGF1 alpha) and the thromboxane A2 metabolite (thromboxane B2). The effect of reducing oxygen tension on both basal mediator release and release triggered by goat antihuman immunoglobulin E was studied. Reducing pO2 of buffer in which lung fragments were placed from 161 to 54 mm Hg resulted in no spontaneous release of histamine, PGD2 or peptide leukotrienes. However, hypoxia had a marked effect on mediator release triggered by goat antihuman immunoglobulin E. Although net histamine release was relatively unaffected (control 13.9 +/- 2.7%, hypoxic 12.7 +/- 2.1%), hypoxic treatment resulted in an 89% inhibition of PGD2 release (control 47.7 +/- 17.4 ng/g of lung, hypoxic 5.26 +/- 1.91 ng/g of lung) and an 81% inhibition of peptide leukotriene release (control 22.5 +/- 7.6 ng/g of lung, hypoxic 4.37 +/- 2.4 ng/g of lung). Similar inhibition was seen for non-mast cell-derived mediators, including PGF2 alpha, prostacyclin metabolite and thromboxane B2, and probably for PGE2. We conclude that hypoxic treatment of human lung fragments in vitro results in no spontaneous release of preformed or newly formed mediators but that it markedly alters mediator release after goat antihuman immunoglobulin E triggering.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Clinical laboratory methods for the assessment and management of human allergic diseases.

The biologic role and clinical relevance of IgE (reaginic) antibodies in immediate-hypersensitivity (allergic) reactions are reviewed, and methods useful in the laboratory diagnosis and management of human allergic diseases are discussed. Quantitative immunoassays for total and allergen-specific IgE antibodies are examined within the context of their use in diagnosis. The radioallergosorbent test inhibition assay and specific IgG antibody immunoassays are described as useful methods in the planning and monitoring of immunotherapy.

Allergens↗
PubMed1985

Mediator release during nasal provocation. A model to investigate the pathophysiology of rhinitis.

The pathogenesis of rhinitis was investigated using a model of nasal provocation with different types of stimuli. Allergic subjects had an immediate response to antigenic challenge with symptoms of rhinitis highly correlated with increments in the concentrations of histamine, prostaglandin D2, kinins and kininogens, leukotrienes, and toluene sulfonyl arginine methyl ester esterase activity in their nasal secretions. This reaction was abated by a tricyclic antihistamine also capable of inhibiting mediator release from human mast cells in vitro and, in some subjects, by disodium cromoglycate. In a number of patients, symptoms reappeared three to 12 hours after nasal provocation. This late reaction also involves release of all of the aforementioned mediators except for prostaglandin D2, and preliminary data suggest that it can be inhibited by oral or topical steroids. Cold, dry air can induce rhinitis with mast cell mediator release from selected subjects. The pathogenesis of this reaction is unclear, but there are indications that osmolarity changes are responsible for mast cell activation. Thus, mast cells can be induced to release mediators and cause nasal symptoms by both immunologic and physical mechanisms, which may account for the pathophysiology of several types of rhinitis.

Air↗
PubMed1985

Inflammatory mediators in late antigen-induced rhinitis.

To investigate the mechanisms responsible for the late-phase response in patients with allergies, we measured four biochemical mediators (histamine, tosyl-L-arginine methyl ester [TAME]-esterase, kinin, and prostaglandin D2) in nasal secretions after nasal challenge with pollen antigen in 12 patients with allergy. Nine patients had an immediate response and a recurrence of symptoms 3 to 11 hours after challenge. The clinical symptoms during recurrence were accompanied by a second increase in levels of histamine, TAME--esterase, and kinin over base-line values, although kinin levels were lower than during the immediate response. In contrast, although the levels of prostaglandin D2 were significantly increased during the immediate response, they did not increase above base line during the late response. Rechallenge with allergen 11 hours after the initial provocation, however, was associated with reappearance of all four biochemical mediators, including prostaglandin D2. We conclude that the late response to nasal challenge with allergen is accompanied by a second increase in the concentrations of histamine and TAME--esterase but differs from the immediate response in the lack of prostaglandin D2 production and in the amount of kinin generated. Since histamine is released only by mast cells and basophils and prostaglandin D2 is not produced by basophils, we suggest that these cells are partly responsible for the late-phase response.

Adult↗
PubMed1985

Naturally occurring carbohydrate antibodies: interference in solid-phase immunoassays.

Antibody assays utilizing carbohydrate matrices (agarose, cellulose) for protein insolubilization are subject to non-specific and specific interfering factors. This report examines factors which diminish the quality of particle-based solid-phase radioimmunoassays (SPRIAs) for antigen-specific human IgG. Interfering factors are divided into (a) constant non-specific binding which is similar with all human sera and appears related to simple adherence of IgG to agarose and cellulose, and (b) absorbable binding which varies considerably among sera in agarose and cellulose-based assays, and results from the presence of IgG antibody specific for the carbohydrate matrix. Constant non-specific binding is predictably 1-3% Bmax (maximum binding) in all human and rabbit sera. In contrast, the absorbable binding levels vary widely: 0.75-29% Bmax in 58% (study 1, n = 50) and 40% (study 2, n = 200) of normal individuals for agarose, and 3-30% Bmax in 70% of the population for microcrystalline cellulose. IgG anti-agarose antibodies were found in 13 of 16 rabbit sera examined. Ultracentrifugation and immune-complex studies demonstrated that aggregated or immune-complexed IgG does not contribute to the absorbable IgG binding. Inhibition with acid hydrolyzed soluble agarose and provided evidence for a specific IgG anti-agarose antibody that causes variable background binding. Pre-absorption of sera with agarose prior to analysis in the agarose-based SPRIA removed greater than 90% of anti-agarose antibodies and eliminated false positive results. These studies suggest rabbit and perhaps other heterologous antibodies prepared by protein-agarose affinity column chromatography may contain significant levels of naturally occurring antibodies against agarose or cellulose. These naturally occurring carbohydrate antibodies may interfere in solid-phase carbohydrate-based immunologic methods and immunoassays.

Antibody Specificity↗
PubMed1985

Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics.

The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated. Antibodies to aztreonam, penicillin, and cephalothin were raised in rabbits. The ability of the homologous or heterologous drug or drug conjugates to inhibit antibody binding was assessed in a solid-phase radioimmunoassay. Aztreonam demonstrated very little ability to interact with anti-penicillin or anti-cephalothin antibodies as it required 10,000-fold higher concentrations than other beta-lactams to achieve equivalent blocking. Similarly, penicillin and cephalothin conjugates did not cross-react, to any significant degree, with anti-aztreonam rabbit antiserums. Interestingly, free aztreonam was as effective as conjugated aztreonam in reacting with antibodies raised against conjugated aztreonam. This result suggested that, in contrast to the other beta-lactams, antibodies to aztreonam recognize the side chain rather than the nuclear structures. Studies with other beta-lactam analogs confirmed that the IgG rabbit anti-aztreonam binding was indeed side chain-specific. Thirty-six volunteers were given a seven-day course of therapeutic doses of aztreonam and in none did any detectable IgE anti-aztreonam antibodies develop. Four of these subjects had evidence of preexisting IgG antibodies cross-reactive with aztreonam, but the levels rose in only one patient following drug exposure. This human IgG anti-aztreonam was also directed to the side chain and did not cross-react with cephalothin or penicillin. The ability of aztreonam to cross-react with human IgE to various penicillin determinants was also investigated. Aztreonam determinants analogous to the penicillin determinants (penicillin, penicilloyl, and penicilloate) were constructed and the maximal concentration that did not evoke false-positive skin test results was determined to be 6 X 10(-3) mol/liter. None of 41 patients with documented IgE-reactive skin tests to various penicillin determinants concurrently demonstrated reproducible reactivity to any aztreonam reagents. IgE anti-penicilloyl antibodies from three persons were also tested in vitro for their ability to cross-react with conjugated or free aztreonam. Minimal, if any, reactivity was observed between the IgE anti-penicilloyl and any of the aztreonam materials. These results indicate that there is very little cross-reactivity between the monobactam aztreonam and other beta-lactam antibiotics.

Adult↗
PubMed1985

Inhalation anesthetics augment oxidant-induced pulmonary vasoconstriction: evidence for a membrane effect.

Inhalational anesthetics "fluidize" biologic membranes. Since arachidonate metabolism also occurs in cell membranes, anesthetic agents may modify arachidonic acid mediator production. The authors used the isolated perfused rabbit lung preparation to examine the effects of inhalational anesthetics on the production of arachidonate mediators. The oxidant tert-butyl-hydroperoxide (t-bu-OOH) is known to cause pulmonary vasoconstriction by causing increased production of thromboxane A2 (TxA2). The authors administered three anesthetics (halothane, cyclopropane, and nitrous oxide) of widely different potencies, at different dosages, each to three different groups of preparations and challenged the lungs at each anesthetic dose with t-bu-OOH. They found a dose-related augmentation of the pulmonary vasopressor response to t-bu-OOH. Preparations given t-bu-OOH alone showed no change in response over time. Lungs perfused with indomethacin (5 micrograms . ml-1 in Krebs-Henseleit buffer), ventilated with cyclopropane (2 MAC), and challenged with t-bu-OOH showed almost complete inhibition of the response to t-bu-OOH. Indomethacin at this concentration is a specific inhibitor of cyclooxygenase. The authors also have demonstrated significantly increased perfusate levels of thromboxane B2 (TxB2), the inactive metabolite of TxA2, after oxidant challenge during exposure to 2% halothane compared with TxB2 levels before halothane exposure. The authors believe that the augmented pressor response and mediator production occur because of increased substrate (arachidonic acid) availability induced by anesthetic agent.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Thromboxane-induced pulmonary vasoconstriction: involvement of calcium.

Infusion of tert-butyl hydroperoxide (t-bu-OOH) or arachidonic acid into rabbit pulmonary arteries stimulated thromboxane B2 (TxB2) production and caused pulmonary vasoconstriction. Both phenomena were blocked by cyclooxygenase inhibitors or a thromboxane synthase inhibitor. The increase in pulmonary arterial pressure caused by either t-bu-OOH or arachidonic acid infusion correlated with the concentration of TxB2 in the effluent perfusate. The concentration of TxB2 in the effluent perfusate, however, was always 10-fold greater after arachidonic acid infusion. In the rabbit pulmonary vascular bed lipoxygenase products did not appear involved in the vasoactive response to t-bu-OOH or exogenous arachidonic acid infusion. Calcium entry blockers or a calcium-free perfusate prevented the thromboxane-induced pulmonary vasoconstriction. Calmodulin inhibitors also blocked the pulmonary vasoconstriction induced by t-bu-OOH without affecting the production of TxB2 or prostacyclin. These results suggest that thromboxane causes pulmonary vasoconstriction by increasing cytosol calcium concentration.

Angiotensin II↗
PubMed1985

Effects of imidazole and indomethacin on fluid balance in isolated sheep lungs.

We determined the effects of extracorporeal perfusion with a constant flow (75 ml . min-1 . kg-1) of autologous blood on hemodynamics and fluid balance in sheep lungs isolated in situ. After 5 min, perfusate leukocyte and platelet counts fell by two-thirds. Pulmonary arterial pressure (Ppa) increased to a maximum of 32.0 +/- 3.4 Torr at 30 min and thereafter fell. Lung lymph flow (QL), measured from the superior thoracic duct, and perfusate thromboxane B2 (TXB2) concentrations followed similar time courses but lagged behind Ppa, reaching maxima of 4.1 +/- 1.2 ml/h and 2.22 +/- 0.02 ng/ml at 60 min. Lung weight gain, measured as the opposite of the weight change of the extracorporeal reservoir, and perfusate 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentration increased rapidly during the first 60 min and then more gradually. After 210 min, weight gain was 224 +/- 40 g and 6-keto-PGF1 alpha concentration, 4.99 +/- 0.01 ng/ml. The ratio of lymph to plasma oncotic pressure (pi L/pi P) at 30 min was 0.61 +/- 0.06 and did not change significantly. Imidazole (5 mM) reduced the changes in TXB2, Ppa, QL, and weight and platelet count but did not alter 6-keto-PGF1 alpha, pi L/pi P, or leukocyte count. Indomethacin (0.056 mM) reduced TXB2, 6-keto-PGF1 alpha, and the early increases in weight, Ppa, and QL but did not alter the time courses of leukocyte or platelet counts. Late in perfusion, however, Ppa and QL were greater than in either untreated or imidazole-treated lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Mechanism of hyperoxia-induced pulmonary vascular paralysis: effect of antioxidant pretreatment.

We designed experiments using isolated rabbit lungs to determine the effect of hyperoxia on the pulmonary vasoconstriction caused by the infusion of the lipid peroxide tert-butyl hydroperoxide (t-bu-OOH), which produces vasoconstriction by stimulating the pulmonary synthesis of thromboxane. Exposure to 48-60 h of 100% O2 at 1 ATA markedly reduced the increase in pulmonary artery pressure caused by t-bu-OOH infusion. We also investigated whether the mechanism for the attenuated vasoconstriction was due to altered production of arachidonate mediators or oxidant-induced damage to the contractile mechanism. In addition to infusing t-bu-OOH, which selectively stimulates thromboxane production, we also infused Intralipid, an esterified fatty acid emulsion that stimulates production of both thromboxane and prostacyclin. These experiments were done to study the effect of hyperoxia on prostacyclin synthesis. To determine if antioxidant therapy would prevent the changes in mediator production and vascular reactivity caused by hyperoxia, we pretreated animals with the antioxidants butylated hydroxyanisole (BHA) or vitamin E. The lack of vascular reactivity to t-bu-OOH was not due to a decrease in thromboxane synthesis or an increase in prostacyclin synthesis. Hyperoxia did not affect thromboxane synthesis during basal conditions or after stimulation of synthesis by t-bu-OOH. 100% O2 also did not effect the basal synthesis of prostacyclin by the lung. Hyperoxia did, however, markedly reduce prostacyclin synthesis when it was stimulated by Intralipid infusion. Antioxidant pretreatment did not reverse the inhibition of prostacyclin synthesis but did prevent the loss of vascular reactivity caused by hyperoxia. Thus hyperoxia causes vascular paralysis through oxidant-induced injury to the pulmonary vasculature.

Animals↗
PubMed1985

Effect of seasonal ragweed exposure on immunoglobulin E antiragweed antibodies in cultures of peripheral mononuclear cells, plasma and nasal secretions.

To determine the effects of seasonal ragweed exposure on in vitro IgE antibody production, the antiragweed IgE antibody content of 7-day cultures of peripheral blood mononuclear cells was assessed in samples obtained before, during and after the ragweed season, in 4 ragweed-allergic and 11 nonallergic individuals. The levels of ragweed-specific IgE and total IgE in unstimulated culture supernatants were measured by solid phase radioimmunoassays. Antiragweed IgE antibody was apparently detectable in the 7-day culture supernatants of both allergic and nonallergic individuals, and the antibody concentrations increased after natural ragweed exposure. However, the bindable counts of IgE antibody in supernatants from allergic patients were inhibited by soluble ragweed antigen, while those from nonallergics were not inhibitable, suggesting that supernatants from nonallergics did not contain true ragweed-specific IgE antibody. Because, for most subjects, the quantity of IgE in culture supernatants from 7-day cultures of living cells was the same as that derived from cells which were either frozen and thawed prior to culture, or briefly exposed to pH 3.7 buffer, the majority of IgE antibody in supernatants from allergic subjects, and of total IgE in supernatants from all subjects, was apparently not newly synthesized, but was preformed, and appeared to be largely derived from the cell surface. IgE antiragweed antibody was detected in the nasal secretions and plasma of allergic, but not nonallergic individuals, and the levels of antibody in allergic subjects increased after seasonal exposure. The fraction of total IgE protein accounted for by IgE antiragweed antibody in nasal secretions collected postseasonally was higher than that in both culture supernatants and plasma, suggesting that ragweed-specific IgE antibody is synthesized locally in the nose.

Antibody Affinity↗
PubMed1985

High-frequency ventilation attenuation of hypoxic pulmonary vasoconstriction. The role of prostacyclin.

In order to determine the effects of high-frequency ventilation on the pulmonary vascular response to hypoxia, we assessed pulmonary vascular resistance at 2 levels of inspired oxygen tension (PlO2), 200 and 30 mmHg, during conventional and high-frequency ventilation in the isolated, blood-perfused lungs of 10 sheep, 5 treated with indomethacin (40 micrograms/ml of perfusate) and 5 untreated. Resistance was assessed by measuring pulmonary artery pressure-flow curves generated over a wide range of flows (20 to 140 ml X min-1 X kg body wt-1). Conventional ventilation was provided by an animal ventilator at a rate of 10 min-1 and a tidal volume of 10 ml X kg body wt-1. High-frequency ventilation was provided by a flow interrupter at a rate of 1,200 min-1 and a tidal volume less than 1.5 ml X kg body wt-1. In the 5 untreated lungs, the normoxic pressure-flow curve was unaltered by high-frequency ventilation, but the hypoxic pulmonary vasoconstrictor response was significantly attenuated. Furthermore, the net rate of change of 6-keto-prostaglandin F1 alpha concentration in the perfusate during hypoxia was significantly greater with high-frequency ventilation (65.4 +/- 8.9 pg X ml-1 X min-1) than with conventional ventilation (2.8 +/- 18.7 pg X ml-1 X min-1). In the 5 indomethacin-treated lungs, production of 6-keto-prostaglandin F1 alpha was markedly depressed, and the attenuation of the hypoxic vasoconstrictor response by high-frequency ventilation was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The pharmacologic modulation of the release of arachidonic acid metabolites from purified human lung mast cells.

Although cyclooxygenase and lipoxygenase inhibitors have been widely used in studies of allergic and inflammatory disorders, the effect of these agents has not been determined on mediators released from purified human lung mast cells. The release of histamine, prostaglandin D2, leukotriene C4, leukotriene B isomers, 5-hydroxyeicosatetraenoic acid (5-HETE), and free arachidonic acid (AA) from preparations of purified human lung mast cells (90 +/- 2% pure) prelabeled with 3H-AA as modified by indomethacin, eicosatriynoic acid (ETI), and diethylcarbamazine (DEC) was determined. Indomethacin (3 microM) markedly (greater than 90%) inhibited the anti-IgE- and ionophore A23187-induced release of PGD2 from these cells but had no effect on the release of histamine or other AA metabolites. Specifically, no increase in LTC production was noted, and no large amount of shunting of products into those produced by lipoxygenases was noted. The ETI, a lipoxygenase inhibitor in many systems, inhibited the release of histamine, PGD2, LTC, LTB isomers, 5-HETE, and free AA, all with an IC50 between 3 and 10 microM. The lack of specificity for lipoxygenase products together with a similar potency for inhibition of histamine release suggests that ETI may act at an early event in the activation process of these cells, apparently prior to the action of phospholipase(s), which releases AA from cellular stores. The DEC inhibited PGD2 release in purified mast cells and histamine release in pure and crude preparations of mast cells, both with IC50 values ranging from 1 to 3 mM. No specificity for enzymes responsible for the production of LTA4 was observed in these cells, unlike the results reported in other systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonate Lipoxygenases↗
PubMed1985

Nasal challenge with cold, dry air results in release of inflammatory mediators. Possible mast cell involvement.

The purpose of our study was to assess the effect of cold, dry air (CDA) on the nasal mucosa of selected individuals in relation to the release of inflammatory mediators associated with mast cells. 12 subjects with a history of nasal symptoms of rhinorrhea and congestion upon cold or dry environmental exposure were challenged by nasal breathing of CDA and warm, moist air (WMA). Each subject was tested on two occasions with the order of the challenges reversed. Symptom scores were recorded, and the levels of histamine, prostaglandin (PG) D2, kinins, and [3H]-N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity in nasal lavage fluids were measured. CDA caused a significant increase in mediator levels and in symptom scores as compared to baseline or to WMA. No significant increase in symptom scores or mediators was noted after WMA challenge, with the exception of a marginal increase in kinins. The response to CDA was similar, regardless of challenge order. Changes in mediators correlated with one another, and symptom scores correlated significantly with the levels of histamine, kinins, and PGD2. Five subjects without a history of nasal symptoms on cold air exposure had no change in mediators or symptom scores after CDA or WMA challenge. We conclude that CDA causes the release of inflammatory mediators possibly associated with mast cells and speculate that such a mechanism may be involved in the bronchospasm induced by CDA in asthmatics.

Adolescent↗
PubMed1985

Nasal challenge with ragweed pollen in hay fever patients. Effect of immunotherapy.

Challenge of the nasal mucosa of allergic subjects with specific allergen induces not only the expected sneezing and rhinorrhea, but also the appearance in nasal secretions of mediators commonly associated with activation of mast cells or basophils: histamine, leukotrienes, prostaglandin D2 (PGD2), kinins, and TAME ([3H]-N-alpha-tosyl-L-arginine methyl ester)-esterase. To determine whether specific immunotherapy alters mediator release in vivo, nasal pollen challenge was used to compare 27 untreated highly sensitive ragweed (RW)-allergic subjects with 12 similarly sensitive patients receiving long-term immunotherapy (3-5 yr) with RW extract (median dose, 6 micrograms RW antigen E). The two groups were equally sensitive based on skin tests and basophil histamine release. The immunized group had a diminished response as demonstrated by (a) the treated group required higher pollen doses to excite sneezing or mediator release; (b) significantly fewer subjects in the treated group released mediators at any dose (TAME-esterase [P = 0.005], PGD2 [P = 0.04]), and (c) the treated group released 3-5-fold less mediator (TAME-esterase [P = 0.01], and histamine [P = 0.02]).

Adult↗