Nasal Administration (nasal + administration)

Distribution by Scientific Domains


Selected Abstracts


Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice

IMMUNOLOGY, Issue 2 2010
Baojing Lu
Summary Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine,phosphate,guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design. [source]


Nasal administration of low molecular weight heparin

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002
John Arnold
Abstract The main objective of this study was to determine if the systemic absorption of therapeutic amounts of heparin was possible following nasal administration. Sprague-Dawley rats received nosedrops containing a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) formulated with or without tetradecylmaltoside (TDM). TDM is a nonionic surfactant that has been previously shown to be a potent absorption enhancer in studies with peptide drugs. LMWH/UFH absorption was determined by measuring plasma anti-Factor Xa activity. The inclusion of 0.25% TDM in nasal formulations containing LMWH resulted in a significant increase in the Cmax and area under the curve (AUC) of anti-Factor Xa activity when compared to LMWH formulated in saline alone. The addition of TDM to a nasal formulation containing UFH resulted in a much smaller increase in the Cmax and the AUC of anti-Factor Xa activity. The absolute bioavailability of LMWH was increased from 4.0,,0.4% in the absence of TDM to 19,,0.3% in the presence of TDM. The reversibility of the absorption enhancing effect of TDM was studied by applying LMWH nasally 60 or 120 min after the enhancer. The effect of TDM on the nasal epithelia appeared to be rapidly reversible. In conclusion, nasal delivery of LMWH, but not UFH, was successful when an absorption enhancer was included to increase nasal permeability. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1707,1714, 2002 [source]


Nasal administration of albuterol: an alternative route of delivery

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2004
Anwar A. Hussain
The use of metered-dose inhalers for the delivery of albuterol, a ,2 -selective adrenergic agonist, is associated with drawbacks, especially in children and the elderly. This investigation was designed to assess the effectiveness of albuterol delivered intranasally and to compare this delivery route with intratracheal and intravenous delivery. Three parameters of pulmonary function (peak maximal expiratory flow, maximal expiratory flow at 50% vital capacity, and total lung capacity) in anaesthetized, artificially ventilated guinea pigs were used to determine the degree of protection produced by albuterol against bronchoconstrictor responses provoked by acetylcholine. The heart rate was also measured. Although intranasal albuterol induced a slower protective action during the very initial phase of absorption, the drug was shown to be equally effective when administered either intranasally or intratracheally. In contrast, despite a significant effect initially in the case of intravenous albuterol, its ability to influence pulmonary function faded rather rapidly. No statistically significant differences in heart rate could be detected among the different treatment groups. In conclusion, intranasal albuterol may offer an alternative to metered-dose inhalers for the treatment of acute bronchospasm and for prevention of exercise-induced asthma, especially for children and the elderly. [source]


Nasal CpG oligodeoxynucleotide administration induces a local inflammatory response in nonallergic individuals

ALLERGY, Issue 9 2009
A. Mnsson
Background:, We have previously demonstrated the presence of toll-like receptor 9 in the nasal mucosa of both healthy and allergic individuals. CpG motifs, found in bacterial and viral DNA, elicit strong immunostimulatory effects via this receptor. CpG is known to skew the immune system towards a T helper 1 (Th1) profile, thereby suppressing Th2-driven allergic responses. This study was designed to examine the effects of CpG administration in the human nose. Methods:, Twenty subjects, of whom 10 suffered from seasonal allergic rhinitis (AR), were challenged intranasally with CpG outside pollen season. Symptom scores, nasal airway resistance (NAR), and nasal and pulmonary nitric oxide (NO) levels were assayed prior to challenge and 30 min, 6, 24 and 48 h post challenge. The presence of leukocytes and various cytokines were analyzed in nasal lavage (NAL) fluids before and after CpG exposure. Results:, Increased NAR, nasal NO production and secretion of interleukin (IL)-1,, IL-6, and IL-8 were seen after CpG exposure. Further analysis revealed that this inflammatory response was more marked in healthy subjects than among patients with AR, although a higher basal inflammatory response was recorded in the allergic group. In vitro experiments suggest that the effects induced by CpG are mediated by epithelial cells and neutrophils. Conclusion:, Nasal administration of CpG induces a local airway inflammation, more distinct among healthy than allergic individuals. The reduced responsiveness to CpG in allergic patients might be related to the ongoing minimal persistent inflammation. Results from cytokine analyses reflect the ability of CpG to induce a pro-inflammatory Th1-like immune response. [source]


Intranasal absorption of sumatriptan and naratriptan: no evidence of local transfer from the nasal cavities to the brain arterial blood in male rats

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2001
Niels Einer-Jensen
Abstract Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. This model was used to investigate whether the antimigraine 5HT1B/1D receptor agonists sumatriptan and naratriptan may also be transferred by the system. The ratio of ,head':,heart' plasma concentrations obtained from two carotid catheters after intranasal administration was not different from 1.00 for either compound, and thus, there was no experimental evidence of a preferential local transfer of drug from the nose to the carotid artery circulation. However, plasma concentrations increased from the first minute after intranasal dosing suggesting that sumatriptan and naratriptan are absorbed into the general systemic circulation from the nasal cavity in rats in a first-order fashion with no lag time. This is consistent with the clinical onset of efficacy of sumatriptan after an intranasal dose which occurs as early as 15 min post dose. Copyright 2001 John Wiley & Sons, Ltd. [source]


Production of a recombinant cholera toxin B subunit-insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetes

BIOTECHNOLOGY & BIOENGINEERING, Issue 7 2005
Yoshikazu Yuki
Abstract Mucosally induced tolerance is an attractive strategy for preventing or reducing autoimmune diseases. Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9,23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion-expression system. Receptor-competitive assay showed that the CTB-insulin peptide binds to GM1 receptor almost equivalent degree as the native form of CTB. Non-obese diabetes (NOD) mice that spontaneously develop an insulin-dependent diabetes were nasally immunized with CTB-insulin peptide (5 g) for three times. The nasal treatment significantly reduced the development of insulin-dependent diabetes and peptide specific DTH responses after systemic immunization with the insulin peptide B 9,23(C19S) in CFA. Nasal administration of as high as 50 g of the peptide alone demonstrated a similar level of the disease inhibition. In contrast, all mice given 5 g of the insulin peptide alone or 5 g of insulin peptide with 25 g of the free form of CTB did not lead to the suppression of diabetes development and DTH responses. Because molecular weight of the insulin peptide is about one tenth of that of the CTB-insulin peptide, the results demonstrate that the recombinant hybrid of autoantigen and CTB increased its tolerogenic potential for nasal administration by up 100-fold on molar base of autoantigen peptide. Taken together, nasally-induced tolerance by administration of the recombinant B.choshinensis -derived hybrid protein of CTB and autoantigen T cell-epitope peptide could be useful mucosal immunetherapy for the control of T cell-mediated autoimmune diseases. 2005 Wiley Periodicals, Inc. [source]


Basal TSH levels compared with TRH-stimulated TSH levels to diagnose different degrees of TSH suppression: diagnostic and therapeutic impact of assay performance

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002
M. Christ-Crain
Abstract Background The estimated prevalence of endogenous subclinical hyperthyroidism varies from 4% to 6% and a basal thyroid stimulating hormone (TSH) level < 05 mU L,1 may be associated with increased mortality in subjects over 60 years of age who are not on thyroid medication. Exogenous TSH suppression is a mainstay in the treatment of thyroid cancer. Because of recent concerns about potential adverse effects, especially of endogenous TSH suppression on bone, the cardiovascular system and cognitive functions, subclinical hyperthyroidism obtained new clinical importance. We therefore re-evaluated the diagnostic value of basal and thyrotrop in TRH-stimulated serum TSH measurements using TSH assays with different sensitivities. Materials and methods A total of 805 oral and nasal TRH stimulation tests were performed on 409 ambulatory subjects with low basal serum TSH concentrations of less than 01 mIU L,1. Basal serum TSH was measured either using a second generation assay (functional sensitivity > 003 mIU L,1) or two third generation assays (functional sensitivity 001 mIU L,1 and 0007 mU L,1, respectively). Serum TSH concentration was determined before and 3 h after oral administration of 40 mg of TRH and before and 30 min after nasal administration of 2 mg of TRH. Results In the oral testing group, the basal TSH levels measured by the different TSH assays were 006 003, 004 002 and 003 002, respectively, whereas the peak TSH levels were 04 06, 04 06 and 03 05 in the patients with subclinical hyperthyroidism. In overt hyperthyroidism, the basal TSH levels were 006 002, 003 002 and 003 002, whereas the peak TSH levels were 019 03, 016 03 and 015 02, respectively. Basal TSH values could discriminate between different degrees of TSH suppression if measured with a third generation assay (P < 0001), but not with a second generation assay. There was only a weak correlation between basal TSH and peak TSH when measured by a second generation assay (n = 126; r = 03; P < 0001) in contrast to the strong correlation found using the third generation assays (n = 128; r = 07; P < 0001 and n = 69; r = 08; P < 0001, respectively). Conclusions In view of the recent concerns about potential adverse effects in TSH suppression and based on our data, it is mandatory to select a TSH assay with a functional sensitivity of , 001 mIU L,1 for optimal titration of L-T4 suppressive therapy, especially in patients with thyroid cancer. If, however, only a second generation TSH assay is available, additional TRH testing allows a more careful titration of suppressive thyroxine therapy. [source]


Primary microparticles and agglomerates of morphine for nasal insufflation

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2006
Paola Russo
Abstract The aim of this work was to study the characteristics of powders of morphine HCl suitable for nasal administration to be employed for pain treatment as alternative to injection. Primary microparticles of morphine were prepared by spray drying of aqueous drug solutions using sugars or sugar derivatives as drying protectors and particle shapers. The spray drying procedure modified morphine crystallinity making the substance amorphous and affecting its stability in dependence on the excipient employed. A tendency of the spray-dried powders to turn to varying degrees of yellow was observed. Tumbling the powder in a rotating pan allowed the agglomeration of the primary microparticles. Agglomerates were also obtained by tumbling a mixture of morphine crystals and spray-dried microparticles of excipients, with advantages for the stability of the preparation. A nasal device quantitatively insufflated all the morphine agglomerates. The in vitro transport of morphine through rabbit nasal mucosa was faster using nasal powders than with the saturated solution of morphine. Lactose was the most effective excipient for agglomerate manufacturing and delivery of spray-dried morphine. The agglomerates of morphine crystals mixed with mannitol/lecithin microparticles showed superior stability. However, the drug permeation through rabbit mucosa was slower than with spray-dried morphine microparticle agglomerates. 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2553,2561, 2006 [source]


Nasal administration of low molecular weight heparin

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002
John Arnold
Abstract The main objective of this study was to determine if the systemic absorption of therapeutic amounts of heparin was possible following nasal administration. Sprague-Dawley rats received nosedrops containing a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) formulated with or without tetradecylmaltoside (TDM). TDM is a nonionic surfactant that has been previously shown to be a potent absorption enhancer in studies with peptide drugs. LMWH/UFH absorption was determined by measuring plasma anti-Factor Xa activity. The inclusion of 0.25% TDM in nasal formulations containing LMWH resulted in a significant increase in the Cmax and area under the curve (AUC) of anti-Factor Xa activity when compared to LMWH formulated in saline alone. The addition of TDM to a nasal formulation containing UFH resulted in a much smaller increase in the Cmax and the AUC of anti-Factor Xa activity. The absolute bioavailability of LMWH was increased from 4.0,,0.4% in the absence of TDM to 19,,0.3% in the presence of TDM. The reversibility of the absorption enhancing effect of TDM was studied by applying LMWH nasally 60 or 120 min after the enhancer. The effect of TDM on the nasal epithelia appeared to be rapidly reversible. In conclusion, nasal delivery of LMWH, but not UFH, was successful when an absorption enhancer was included to increase nasal permeability. 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1707,1714, 2002 [source]


The use of simple dynamic mucosal models and confocal microscopy for the evaluation of lyophilised nasal formulations

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2007
Fiona McInnes
A range of methods is reported in the literature for assessing hydration and adhesion parameters in the performance of nasal bioadhesive formulations; however, these tests do not always represent the dynamic conditions in the nasal cavity. Lyophilised formulations intended for nasal administration were evaluated using in-vitro tests designed in an attempt to mimic relevant processes in the nasal cavity, and intended to discriminate between different formulations. Initial investigative studies using scanning electron microscopy revealed that the lyophilisate had a highly porous internal structure, expected to provide an ideal porous pathway for re-hydration. Vapour sorption analysis demonstrated substantial weight gain of the lyophilisates on exposure to 95% relative humidity, ranging from 38% to 66%. Agar was used as a synthetic mucosal model designed to provide a standardised quantity of water available for rehydration of the formulations in in-vitro tests. A dynamic adhesion test and a texture analyser sliding test were designed to quantify different aspects of the spreading and adhesion of the hydrating formulations on the synthetic mucosal surface. Examination of the lyophilised formulations using confocal microscopy allowed visualisation and quantification of the initial rate of water ingress into the lyophilisates, which was found to consist of an initial rapid phase, followed by a slower steady-state phase. The results demonstrated that the use of a combination of methods representing the dynamic conditions of the nasal cavity is advisable in order to evaluate a formulation fully and to avoid misleading conclusions. [source]


Evaluation of the immune response induced by a nasal anthrax vaccine based on the protective antigen protein in anaesthetized and non-anaesthetized mice

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2006
Brian R. Sloat
To better protect against inhalational anthrax infection, a nasal anthrax vaccine based on the protective antigen (PA) protein of Bacillus anthracis could be an attractive alternative to the current Anthrax-Vaccine-Adsorbed (AVA), which was licensed for cutaneous anthrax prevention. Previously, we have demonstrated that an anti-PA immune response comparable with that in mice subcutaneously immunized with PA protein adjuvanted with aluminium hydroxide was induced in both the systemic compartment and the mucosal secretions of the nose and lung of anaesthetized mice when they were nasally immunized with PA protein incorporated into previously reported LPD (Liposome,Protamine,DNA) particles. In this study, we evaluated the anti-PA immune response induced by the nasal PA/LPD particles in non-anaesthetized mice and compared it with that in anaesthetized mice. Our data showed that the anti-PA antibody response and the anthrax lethal toxin-neutralization activity induced by the nasal PA/LPD in non-anaesthetized mice was relatively weaker than that in anaesthetized mice. However, the splenocytes isolated from the nasally immunized mice, anaesthetized and non-anaesthetized, proliferated comparably after in-vitro re-stimulation. By evaluating the uptake of fluorescence-labelled LPD particles by phagocytes in the nasal and broncho-alveolar lavages of mice after the nasal administration, we concluded that the relatively weaker anti-PA immune response in the non-anaesthetized mice might be partially attributed to the reduced retention of the PA/LPD particles in the nasal cavity of the non-anaesthetized mice. Data collected in this study are expected to be useful for future anthrax nasal vaccine studies when mice are used as a model. [source]


Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2005
Elisabetta Gavini
Microparticulate delivery systems designed for the nasal administration of an antiemetic drug, metoclopramide hydrochloride, were prepared. Microspheres composed of sodium alginate, chitosan hydrochloride, or both, were obtained using a spray-drying method; some batches of drug-free microparticles were prepared as a comparison. The morphology, in-vitro swelling behaviour, mucoadhesive properties and drug release from microparticles were evaluated. Ex-vivo drug permeation tests were carried out using sheep nasal mucosa; permeation test of the drug solution was peformed as comparison. During ex-vivo permeation tests, transmission electron microscopy (TEM) analyses were carried out on the nasal mucosa to study the morphological changes of epithelial cells and tight junctions, while the change in microsphere morphology was examined using photostereo microscopy (PM). Spray-dried microparticles had a mean diameter (dvs) in the range of about 3,10 ,m. They showed good in-vitro mucoadhesive properties. In-vitro release profiles and swelling behaviour depended on their composition: the drug release occurred in 1,3 h. Ex-vivo studies showed that drug permeation through the mucosa from microparticles based on chitosan was higher than from those consisting of alginate alone. This can be related to the penetration enhancing properties of chitosan. Complexation of chitosan with alginate led to a control of the drug release. Microscopy observation of microspheres during the permeation tests revealed that microparticles swelled and gelled, maintaining their shape. TEM analyses of the mucosa after exposure to the microparticles consisting of alginate/chitosan showed opened tight junctions. This preliminary study shows that alginate/chitosan spray-dried microspheres have promising properties for use as mucoadhesive nasal carriers of an antiemetic drug. [source]


The biopharmaceutical aspects of nasal mucoadhesive drug delivery

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2001
Michael Ikechukwu Ugwoke
Nasal drug administration has frequently been proposed as the most feasible alternative to parenteral injections. This is due to the high permeability of the nasal epithelium, allowing a higher molecular mass cut-off at approximately 1000 Da, and the rapid drug absorption rate with plasma drug profiles sometimes almost identical to those from intravenous injections. Despite the potential of nasal drug delivery, it has a number of limitations. In this review, the anatomy and physiology of the nasal cavity, as well as ciliary beating and mucociliary clearance as they relate to nasal drug absorption, are introduced. The rationale for nasal drug delivery and its limitations, some factors that influence nasal drug absorption, and the experimental models used in nasal drug delivery research are also reviewed. Nasal mucoadhesion as a promising method of nasal absorption enhancement is discussed, and factors that influence mucoadhesion, as well as safety of nasal mucoadhesive drug delivery systems are reviewed in detail. Nasal drug administration is presently mostly used for local therapies within the nasal cavity. Anti-allergic drugs and nasal decongestants are the most common examples. However, nasal drug administration for systemic effects has been practised since ancient times. Nasally-administered psychotropic drugs by native Americans, the use of tobacco snuffs, and nasal administration of illicit drugs such as cocaine are all well known (Illum & Davis 1992). Nowadays, the nasal cavity is being actively explored for systemic administration of other therapeutic agents, particularly peptides and proteins (Illum 1992; Edman & Bjork 1992), as well as for immunization purposes (Lemoine et al 1998). To better understand the basis for nasal drug absorption and factors that can influence it, a brief review of the anatomy and physiology of the nose is appropriate. [source]


Induction of immune responses and prevention of alveolar bone loss by intranasal administration of mice with Porphyromonas gingivalis fimbriae and recombinant cholera toxin B subunit

MOLECULAR ORAL MICROBIOLOGY, Issue 6 2007
Y. Takahashi
Introduction:, Adult periodontitis is initiated by specific periodontal pathogens represented by Porphyromonas gingivalis; however, an effective measure for preventing the disease has not yet been established. In this study, the effectiveness of a vaccine composed of fimbriae of P. gingivalis and recombinant cholera toxin B subunit (rCTB) was evaluated using BALB/c mice. Methods:, Fimbriae and rCTB were co-administered intranasally to BALB/c mice on days 0, 14, 21, and 28. On day 35, mice were sacrificed to determine immunoglobulin levels in serum, saliva, and nasal and lung extracts by enzyme-linked immunosorbent assay. The prevention effect of the vaccine on P. gingivalis -induced periodontitis in mice was evaluated by measuring alveolar bone loss. Results:, The rCTB significantly increased serum immunoglobulin (Ig)A levels when mice were administered with a minimal amount (0.5 ,g) of the fimbrial antigen. The adjuvant effect on serum IgG production was indistinct because the minimal amount of the antigen still induced a large amount of IgG. In contrast to systemic responses, a fimbria-specific secretory IgA response was strongly induced by co-administration of rCTB and 0.5 ,g fimbriae; the same amount of the antigen alone scarcely induced a response. Histopathological examination revealed IgA-positive plasma cells in the nasal mucosal tissue but no observable mast cells in the area. In addition, nasal administration of the fimbrial vaccine significantly protected the mice from P. gingivalis -mediated alveolar bone loss. Conclusion:, Nasal vaccination with a combination of fimbriae and rCTB can be an effective means of preventing P. gingivalis -mediated periodontitis. [source]


Production of a recombinant cholera toxin B subunit-insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetes

BIOTECHNOLOGY & BIOENGINEERING, Issue 7 2005
Yoshikazu Yuki
Abstract Mucosally induced tolerance is an attractive strategy for preventing or reducing autoimmune diseases. Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9,23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion-expression system. Receptor-competitive assay showed that the CTB-insulin peptide binds to GM1 receptor almost equivalent degree as the native form of CTB. Non-obese diabetes (NOD) mice that spontaneously develop an insulin-dependent diabetes were nasally immunized with CTB-insulin peptide (5 g) for three times. The nasal treatment significantly reduced the development of insulin-dependent diabetes and peptide specific DTH responses after systemic immunization with the insulin peptide B 9,23(C19S) in CFA. Nasal administration of as high as 50 g of the peptide alone demonstrated a similar level of the disease inhibition. In contrast, all mice given 5 g of the insulin peptide alone or 5 g of insulin peptide with 25 g of the free form of CTB did not lead to the suppression of diabetes development and DTH responses. Because molecular weight of the insulin peptide is about one tenth of that of the CTB-insulin peptide, the results demonstrate that the recombinant hybrid of autoantigen and CTB increased its tolerogenic potential for nasal administration by up 100-fold on molar base of autoantigen peptide. Taken together, nasally-induced tolerance by administration of the recombinant B.choshinensis -derived hybrid protein of CTB and autoantigen T cell-epitope peptide could be useful mucosal immunetherapy for the control of T cell-mediated autoimmune diseases. 2005 Wiley Periodicals, Inc. [source]


Influence of viral infection on the development of nasal hypersensitivity

CLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2005
Y. Okamoto
Summary Background The underlying relationship between viral infections and allergic diseases of the upper respiratory tract has not been well clarified. Methods In order to clarify the relationship between viral infection and nasal hypersensitivity, mice were sensitized with ovalbumin (OVA) and then infected intranasally with respiratory syncytial virus (RSV), after which their nasal sensitivity to histamine or antigen was examined. Results Non-sensitized mice showed transient mild nasal hypersensitivity following nasal administration of histamine after intranasal RSV inoculation. In mice sensitized with OVA, RSV infection significantly exaggerated their nasal hypersensitivity to histamine and OVA. Treatment of these mice with a neurokinin (NK)-1/NK-2 receptor antagonist, but not with anti-IL-5 antibodies, reduced their hypersensitivity. The infiltration of nasal mucosa with eosinophils was temporarily associated with accelerated rate of RSV elimination in these animals. Conclusion RSV infection induced transient nasal hypersensitivity. Several mechanisms, including impairment of nasal epithelial cells are thought to mediate this effect. In allergen-sensitized mice, RSV inoculation strongly enhanced nasal hypersensitivity. [source]