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[Immunoenzyme analysis of post-vaccination secretory immunity to influenza A and B viruses using a manufactured monoclonal immunoenzyme test system].

The formation of postvaccinal secretory immunity to influenza A and B viruses was studied by a new monoclonal enzyme immunoassay test system for measuring specific secretory IgA in young people vaccinated with live cold-adapted vaccines (LCAV) intranasally and with inactivated commercial centrifuged influenza vaccine (IIV) parenterally, intranasally, and orally. Secretory IgA most intensively accumulated in subjects intranasally vaccinated with LCAV, less so in subjects vaccinated with IIV intranasally and orally, and just negligibly in those vaccinated with IIV parenterally. In vaccinees immunized with LCAV intranasally the intensity of immune secretory response depended on the initial concentrations of specific IgA before vaccination. Intranasal administration of LCAV in the presence of high concentrations of secretory IgA led in some subjects either to a decrease in the incidence of conversions or to a 2-8-fold drop of their initial titers. Parenteral injection of IIV caused the most expressed suppression of the immune response in the secretory immunity system. Use of biological stimulant adaptogen increased 2.2 times the incidence of conversions of secretory IgA in subjects intranasally vaccinated with LCAV.

Administration, Intranasal↗

Overweight humans are resistant to the weight-reducing effects of melanocortin4-10.

CONTEXT: By enhancing energy expenditure and suppressing appetite, melanocortin peptides derived from proopiomelanocortin play a primary role in the hypothalamic regulation of body weight. In a recent study in normal-weight adults, the 6-wk intranasal administration of the MSH/ACTH(4-10) core fragment of proopiomelanocortin resulted in a distinct reduction of body weight and body fat, accompanied by significant decreases in leptin and insulin plasma concentrations. OBJECTIVE: The present study aimed to generalize this finding to overweight patients. DESIGN, SUBJECTS, AND INTERVENTION: MSH/ACTH(4-10) (0.5 mg) and placebo were intranasally administered once in the morning and once in the evening over a period of 12 wk in 23 overweight men (body mass index, mean +/- sem: 29.72 +/- 0.43 kg/m(2)). RESULTS: MSH/ACTH(4-10) did not induce any significant reduction in body weight, body fat, and plasma levels of insulin and leptin as compared with the effects of placebo. Melanocortin treatment was accompanied by reduced cortisol concentrations. CONCLUSIONS: We conclude that contrasting with normal-weight humans, overweight subjects are not susceptible to the effects of melanocortin administration on hypothalamic weight regulatory systems. In overweight subjects, a decreased sensitivity to ACTH/MSH peptides may derive from alterations at the level of the melanocortin receptor or at subsequent steps in the processing of the body fat signal.

Administration, Intranasal↗

Enhanced permeation of diazepam through artificial membranes from supersaturated solutions.

The present work consists of studies of saturated and supersaturated solutions of diazepam (DZP) in [glycofurol (GF)/water] cosolvent systems, which are a potential dosage form for intranasal administration of DZP in rapid response to epileptic seizure emergencies. Equilibrium solubility of DZP increased in a convex manner with GF content, and also increased with temperature. Rapidly mixed supersaturated 40 mg/mL solutions displayed temporal stability, with long periods before onset of crystallization. Permeation of supersaturated DZP across polydimethylsiloxane (PDMS) membranes, chosen as an in vitro model for nasal mucosa, was shown to be well described by Theeuwes's transference equation, when DZP was formulated up to three times its solubility in a particular cosolvent vehicle. Transference and time lag were independent of vehicle composition, indicating that permeation enhancement was due virtually exclusively to enhanced driving force due to supersaturation. Implications of these results on potential intranasal DZP delivery systems based on supersaturation are discussed.

Administration, Intranasal↗

Comparative trial of large-particle aerosol and nose drop administration of live attenuated influenza vaccines.

Healthy adult subjects (n = 198) were randomized to receive bivalent cold-adapted (ca) influenza A vaccine containing 10(7.4) TCID50 each of A/Kawasaki/9/86 (H1N1) and A/Los Angeles/2/87 (H3N2) by either nose drops (ND) or large-particle aerosol (LPA). All subjects had received monovalent inactivated influenza B vaccine intramuscularly in the previous year. Ninety percent of LPA recipients and 82% of ND recipients preferred intranasal administration to their previous experience with intramuscular vaccine. Twenty-six (27%) of 98 LPA recipients and 47 (49%) of 97 ND recipients reported swallowing vaccine (P = .008). Fever was observed uncommonly (< or = 5%), and incidence of respiratory symptoms was comparable between groups. Fourfold or greater hemagglutination antibody response to at least one of the influenza A vaccine viruses was significantly more frequent after LPA (64%) than ND vaccination (43%; P = .005). LPA administration of ca influenza to the nasopharynx was well tolerated, safe, and more immunogenic than ND delivery.

Administration, Intranasal↗

Hemodynamic effects of intranasal cocaine in humans.

Intranasal cocaine, 2 to 3 mg/kg body weight, is a commonly used local anesthetic for rhinolaryngologic procedures, and many persons who abuse it ingest a similar amount. Previous studies in humans showed that this dose of cocaine causes coronary vasoconstriction, and studies in animals showed that larger amounts given intravenously diminish myocardial performance. This study assessed the hemodynamic effects of intranasal cocaine, 2 mg/kg, in humans. In 15 patients (8 men and 7 women, aged 30 to 70 years) referred for cardiac catheterization, heart rate, systemic arterial pressure, cardiac index, pulmonary capillary wedge and pulmonary artery pressures and left ventricular pressure and its first derivative (dP/dt) were measured before and 15, 30 and 45 min after intranasal administration of saline solution (n = 5) or cocaine, 2 mg/kg (n = 10). No variable changed with saline solution. In those given cocaine, there was an increase in heart rate (17 +/- 16%, mean +/- SD), mean systemic arterial pressure (8 +/- 7%), cardiac index (18 +/- 18%) and positive and negative dP/dt (18 +/- 20% and 15 +/- 22%, respectively) (p less than 0.05 for all). Thus, intranasal cocaine in a dose similar to that used medicinally or "recreationally" does not exert a deleterious influence on intracardiac pressures and left ventricular performance.

Administration, Intranasal↗

Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea-pigs in vivo.

BACKGROUND: Interleukin-8 (IL-8) has been shown to be a chemotactic factor for neutrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which are released from C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. OBJECTIVE: This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness. METHODS: IL-8 at a dose of 5 micrograms/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilated through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to increasing concentrations of inhaled histamine (25, 50, 100, and 200 micrograms/mL). A NK1 and NK2 dual antagonist FK224 (10 mg/kg), a selective NK1 antagonist FK888 (10 mg/kg) or vehicle was intravenously administered 10 min before measurement of bronchial responsiveness. RESULTS: The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness. CONCLUSION: We conclude that repeated intranasal administration of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.

Animals↗

Effect of vaccination on experimental infection with Bordetella bronchiseptica in dogs.

OBJECTIVE: To determine comparative efficacy of vaccines administered IM and intranasally, used alone or sequentially, to protect puppies from infection with Bordetella bronchiseptica and determine whether systemic or mucosal antibody response correlated with protection. DESIGN: Randomized controlled trial. ANIMALS: 50 specific-pathogen-free Beagle puppies. PROCEDURE: In 2 replicates of 25 dogs each, 14-week-old puppies that were vaccinated against canine distemper virus and parvovirus were vaccinated against B bronchiseptica via intranasal, IM, intranasal-IM, or IM-intranasal administration or were unvaccinated controls. Puppies were challenge exposed via aerosol administration of B bronchiseptica 2 weeks after final vaccination. Clinical variables and systemic and mucosal antibody responses were monitored for 10 days after challenge exposure. Puppies in replicate 1 were necropsied for histologic and immunohistochemical studies. RESULTS: Control puppies that were seronegative before challenge exposure developed paroxysmal coughing, signs of depression, anorexia, and fever. Vaccinated puppies (either vaccine) that were seronegative before challenge exposure had fewer clinical signs. Puppies that received both vaccines had the least severe clinical signs and fewest lesions in the respiratory tract. Vaccinated dogs had significantly higher concentrations of B bronchiseptica-reactive antibodies in serum saliva before and after challenge. Antibody concentrations were negatively correlated with bacterial growth in nasal cavity and pharyngeal samples after challenge exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Parenterally and intranasally administered vaccines containing B bronchiseptica may provide substantial protection from clinical signs of respiratory tract disease associated with infection by this bacterium. Administration of both types of vaccines in sequence afforded the greatest degree of protection against disease.

Administration, Intranasal↗

Generation of protective immune responses to plague by mucosal administration of microsphere coencapsulated recombinant subunits.

We have investigated noninvasive immunization to plague. Recombinant subunit antigens, F1 and V from Yersinia pestis, were coencapsulated in biodegradable poly(L100 LD(50's) inhalational challenge with virulent Y. pestis. These data expand on previous findings from our laboratories, providing further insight into the mechanics of safeguarding mice from plague through nasal immunization. Further, these results demonstrate that in a murine model, solid protection from pneumonic plague can be engendered by two intranasal administrations of appropriately formulated recombinant proteins.

Administration, Intranasal↗

Involvement of kinins in hyperresponsiveness induced by platelet activating factor in the human nasal airway.

1. The aim of this study was to investigate the role of kinins in the development of nasal hyperresponsiveness induced by platelet activating factor (PAF) in normal human subjects. 2. Intranasal administration of PAF, 60 micrograms, induced an increased responsiveness to histamine, 200 micrograms per nostril, 6 h later. This effect was abolished by pretreatment with the bradykinin B2 receptor antagonists icatibant and [1-adamantaneacetyl-D-Arg0,Hyp3,beta-(2-thienyl)-Al a5,8,D-Phe7]-bradykinin ([Ad]-BK), both at 200 micrograms, every 2 h following PAF administration. 3. In a separate experiment, utilizing the same protocol, nasal lavage was used to measure the release of mediators into the nasal cavity following treatment with PAF. PAF increased the levels of eosinophil cationic protein (ECP) and kinin detected in the lavage samples, compared with a saline control. The levels of these mediators were reduced by pretreatment with either icatibant or [Ad]-BK. 4. Administration of lyso-PAF, 60 micrograms intranasally, did not cause a rise in kinin or ECP levels in nasal lavage fluid. 5. Exogenous bradykinin, 500 micrograms, or a saline control, applied topically to the nasal mucosa every 30 min for 2 h, failed to cause hyperresponsiveness to histamine. 6. We conclude that bradykinin itself does not cause hyperresponsiveness, but is involved in the hyperresponsiveness induced by PAF in the human nasal airway.

Adamantane↗

New twist on neuronal insulin receptor signaling in health, disease, and therapeutics.

Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.

Animals↗

Pathological aspects of immunization of mice against influenza virus infection.

Groups of mice were immunized against influenza Ao/NWS virus by a single intranasal administration of inactivated homologous virus, by 2 intranasal doses of vaccine separated by an interval of 2 weeks, or by 2 intraperitoneal doses of the same vaccine. When subjected 2 weeks later to a standard challenge of 6 x 10(5) egg infecting units Ao/NWS virus instilled intranasally, mortality fell significantly from 64% in unimmunized mice to 39% in mice given a single intranasal dose of vaccine and to 29% in animals which received double intranasal vaccine. The best protection was conferred by double intraperitoneal immunization, after which mortality was 10%. Immunity waned with time, since the mortality of mice doubly immunized by the respiratory route and challenged 30 weeks later was 49%. Intrapulmonary lymphoid tissue developed in large amounts in a proportion of mice immunized by all methods and challenged after an interval of 2 weeks. Attention is drawn to this reaction as a possible unfavourable consequence of vaccination. There were no lesions in the lungs or central nervous system after immunization without subsequent challenge. The importance of histopathology in vaccine trials in experimental animals is emphasized by the consistently higher detection rate of lesions in lungs by histological examination than by visual inspection alone.

Animals↗

Brain uptake of dihydroergotamine after intravenous and nasal administration in the rat.

This study was conducted to determine the uptake of dihydroergotamine (DHE) into the brain after intravenous and intranasal administration in rats. Eight anesthetized rats received either an intravenous (i.v.) or two successive intranasal (i.n.) doses of tritium labeled dihydroergotamine (3H-DHE) with 14C-inulin as a non-BBB (blood-brain barrier) permeable marker. Radioactivity concentrations in plasma were determined at designated times within 30 min postdose, and in blood and seven brain regions (olfactory bulb, frontal cortex, parietal cortex, occipital cortex, cerebellum, mid-brain areas, and brain stem) at 30 min. The plasma-to-brain permeability*area product (PeA) following an i.v. dose was calculated based on the 30-min brain tissue concentration and the area under the plasma concentration-time curve (AUC0-30 min, i.v.) assuming unidirectional transport from plasma to brain. Direct transport from nasal cavity to brain was assessed based on the amount of radioactivity in brain determined experimentally and predicted based on plasma AUC0-30 min, i.n. and PeA obtained from i.v. data. Following an i.v. dose, DHE distributed into the brain with a brain-to-plasma concentration ratio of approximately 5% at 30 min postdose. The PeA value of DHE ranged from 8.6 x 10(-4) to 37.5 x 10(-4) mL min(-1) g(-1) in different brain regions. Following i.n. doses the experimentally determined concentration in olfactory bulb was approximately 51 times, and in other regions three to seven times, greater than predicted values based only on PeA and plasma AUC, suggesting a direct transport pathway from the nasal cavity to the brain. As a result, the brain tissue concentrations at 30 min were similar to (0.31-1.04 times) those following an i.v. dose except for the olfactory bulb, in which the concentration was approximately four times greater than that following an i.v. dose. In conclusion, 3H-DHE penetrated the BBB following intravenous administration. Following i.n. doses, 3H-DHE was able to enter the brain directly from the nasal cavity, with the olfactory bulb being a part of the direct passage from nasal cavity to brain.

Administration, Intranasal↗

Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis.

Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Intranasal delivery of chitosan-DNA vaccine generates mucosal SIgA and anti-CVB3 protection.

Coxsackievirus B3 infections are common causes of acute and chronic myocarditis with no effective prophylactic treatment available. We describe here a prophylactic strategy using chitosan-DNA intranasal immunization to induce CVB3 specific immune responses. Intranasal administration with chitosan-DNA complex prepared by votexing DNA with chitosan, a natural mucus absorption enhancer, resulted in transgenic DNA expression in mouse nasopharynx. Mice immunized with chitosan-DNA (pcDNA3-VP1) encoding VP1, major structural protein of CVB3, produced much higher levels of serum IgG and mucosal secretory IgA compared to mice treated with pcDNA3-VP1 or pcDNA3. Increased virus-specific cytotoxic activity of spleen cells derived from chitosan-DNA vaccinated mice was also determined. Chitosan-pcDNA3-VP1 intranasal immunization resulted in 42.9% protection of mice against lethal CVB3 challenge and a significant reduction of viral load after acute CVB3 infection. Meanwhile no myonecrosis or infiltrating immune cells indicating ongoing myocarditis was detected in hearts of surviving mice treated with chitosan-DNA. Together, Our data show that intranasal delivery of chitosan-DNA vaccine successfully induced mucosal SIgA secretion and might be a promising vaccine candidate to protect against CVB3 infection.

Administration, Intranasal↗

Intranasal peptide-induced peripheral tolerance: the role of IL-10 in regulatory T cell function within the context of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease commonly employed as a model for multiple sclerosis. Extensive studies have demonstrated that EAE may be prevented or ameliorated by the intranasal administration of soluble peptides representing encephalitogenic epitopes. There is increasing evidence that this peptide administration may function via the generation of regulatory cells. The mechanism of action of these cells remains controversial and it seems likely that it may vary between experimental models. At present the majority of work on regulatory cells has centred on characterising naturally occurring regulators, or those generated artificially ex vivo, and less is known about induced regulatory cells produced following peptide administration. This report aims to briefly outline the evidence for the existence of natural regulatory T cells and to introduce the sub-types of induced regulatory T cells now recognised. In several of these regulatory cell systems investigated to date, interleukin-10 (IL-10) has been shown to be important in cell function. This has not been directly investigated in a model employing peptide therapy to induce peripheral tolerance, hence the purpose of this study was to investigate the role of IL-10 in the generation of these regulatory cells. This work has employed both a TCR transgenic mouse system, for predominantly in vitro studies of cell function, and an IL-10 knock-out mouse strain to investigate in vivo disease protection. The results summarised in this report demonstrate that IL-10 is fundamentally important in the generation of disease protection following intranasal peptide therapy.

Administration, Intranasal↗

Nasal administration of salmon calcitonin for prevention of glucocorticoid-induced osteoporosis in children with nephrosis.

To determine the effect of intranasal administration of salmon calcitonin on glucocorticoid-induced osteoporosis in children with nephrosis, we gave 100 U of calcitonin intranasally on alternate days with 1 alpha-hydroxyvitamin D3 to five children, 8 to 12 years of age, with frequently relapsing nephrosis. Four patients with osteoporosis, 10 to 14 years of age, were treated only with 1 alpha-hydroxyvitamin D3 and served as control subjects. Both groups were treated with an almost equal amount of glucocorticoids previously and during this study period. Bone mineral content of the spine was measured by a quantitative computed tomographic technique. The bone mineral content was preserved in both cortical and spongeous areas of the vertebrae during the 16-month period in the calcitonin-treated group but was decreased significantly in the control group. Urinary hydroxyproline and calcium excretion decreased significantly in the calcitonin-treated group. The serum calcium and phosphorus concentrations and the parathyroid function did not change significantly in either group. We conclude that calcitonin suppressed bone resorption and might be useful for the long-term treatment of osteoporosis, in combination with 1 alpha-hydroxyvitamin D3, in children with nephrosis requiring long-term glucocorticoid therapy.

Administration, Intranasal↗

Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza.

OBJECTIVE: The current study evaluated whether intranasal administration of the sialic acid analog 4-guanidino-Neu5Ac2en (GG167), an inhibitor of influenza virus neuraminidase, was effective and safe in either preventing or treating experimental human influenza. METHODS: Four randomized, double-blind, placebo-controlled trials involving three prophylaxis limbs, two early treatment limbs, and one delayed treatment limb were conducted. SETTING: Isolation in individual rooms. PARTICIPANTS: Susceptible (serum hemagglutination-inhibition antibody titer < or = 1:8) adult volunteers (n = 166) were inoculated intranasally with 10(5) TCID50 influenza A/Texas/91 (H1N1) virus. INTERVENTION: GG167, 3.6 to 16 mg, was administered intranasally two or six times daily beginning 4 hours before inoculation (prophylaxis) or 1 or 2 days afterward (early or delayed treatment). MAIN OUTCOMES: Virological measures were frequency of infection based on viral shedding and/or seroconversion (prophylaxis) or quantitative viral shedding based on titers and duration of virus recovery (treatment). Clinical measures were the frequency of febrile illness and symptom severity scores. RESULTS: Intranasal GG167 was well tolerated for both prophylaxis and therapy. For all dose groups combined, GG167 prophylaxis was 82% effective in preventing laboratory evidence of infection and 95% effective in preventing febrile illness (P < .01 vs placebo). Early treatment with GG167 reduced peak viral titers by 2.0 log10, the median duration of viral shedding by 3 days, and the frequency of febrile illness by 85% (P < .05 for each comparison). Other measures of illness were reduced by approximately 50% to 70% in the GG167 dosing groups. Twice daily dosing was as effective as six times daily. CONCLUSIONS: Direct respiratory administration of the selective neuraminidase inhibitor GG167 appears safe and effective for both prevention and early treatment of experimental influenza. Influenza virus neuraminidase is important for viral replication in humans.

Administration, Intranasal↗

Pharmacokinetics and anti-asthmatic potential of non-parenterally administered recombinant human interleukin-1 receptor antagonist in animal models.

The objectives of this study were to define the pharmacokinetics of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) and its effects on allergic asthma, cell adhesion molecules, and upper respiratory tract following non-parenteral administration in animals. Pharmacokinetics and immunomodulating effects of rhIL-1ra were investigated in Sprague-Dawley rats and asthmatic guinea pigs, respectively. Effects on the upper respiratory tract following the applications of rhIL-1ra were investigated on the ex vivo nasal mucosa of Sprague-Dawley rats and in situ in the upper palate of Chinese toads. Absolute bioavailabilities after intratracheal and intranasal administrations of rhIL-1ra were 94.3% and 24.8%, respectively. After administration of rhIL-1ra solution as ultrasonic spraying, the asthmatic symptom in guinea pigs was obviously attenuated. The plasma soluble intercellular cell adhesion molecule (sICAM-1) and P-selectin levels in asthmatic guinea pigs were each dose-dependently reduced with the increase of rhIL-1ra dose. The rhIL-1ra solution after administration via the airway seemed to have no impact on the integrity of nasal mucosa and mucocilia clearance in the upper respiratory tract. The present study provides evidence that rhIL-1ra effectively suppresses allergen-induced asthmatic symptoms through spraying, which corresponds to nasal and pulmonary absorption or both, and the efficacy is associated with downregulation of sICAM-1 and P-selectin expressions.

Administration, Intranasal↗