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PubMed2006

Prophylactic intranasal treatment with fragments of 1,3-beta-glucanase olive pollen allergen prevents airway inflammation in a murine model of type I allergy.

BACKGROUND: Olive pollen is an important cause of allergy in Mediterranean countries. More than 50% of olive-pollen-allergic patients are sensitized against the 1,3-beta-glucanase Ole e 9. To date, prophylactic and therapeutic treatments using purified recombinant allergens have not been studied in animal models of olive pollen allergy. METHODS: BALB/c mice were immunized against Ole e 9 combining intraperitoneal injections of the allergen in Al(OH)3 with airway allergen challenges. A prophylactic treatment was performed by intranasal administration of a mixture of the recombinant fragments of the allergen prior to Ole e 9 sensitization. Serum levels of specific IgE, IgG1, IgG2a and IgG2b were measured by ELISA, and total IgE levels by sandwich ELISA. Bronchoalveolar lavage and lungs from mice were collected to study airway inflammation by light microscopy. RESULTS: BALB/c mice immunized against Ole e 9 developed a predominantly Th2-like immune response with allergen-specific immunoglobulin induction and airway inflammation accompanied by the infiltration of eosinophils, lymphocytes, and neutrophils in the lung. Prophylactic treatment by intranasal application of the recombinant fragments of Ole e 9 avoids airway inflammation induced by sensitization with this allergen although the levels of Ole e 9-specific antibodies remain unchanged. CONCLUSIONS: Prophylactic intranasal treatment with recombinant fragments of Ole e 9 prevents airway inflammation triggered by immunization to this allergen in a murine model of type I allergy.

Administration, Intranasal↗

PubMed1999

Intranasal IFN-gamma gene transfer protects BALB/c mice against respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a major respiratory pathogen in infants, young children and the elderly and causes severe bronchiolitis and asthma. In an effort to develop a preventive IFN-gamma therapy against RSV infection, an intranasal gene transfer strategy was utilized. Intranasal administration of a plasmid expressing the IFN-gamma cDNA (pIFN-gamma) resulted in the expression of IFN-gamma in murine lungs and decreased RSV replication. The mice administered with pIFN-gamma and then infected with RSV exhibited a significant decrease in broncho-alveolar lavage lymphocyte and neutrophil counts. A significant reduction in epithelial cell damage, infiltration of mononuclear cells in the peribronchiolar and perivascular regions, and thickening of the septa was observed in the lungs of mice treated with pIFN-gamma when compared to controls. These results suggest that intranasal IFN-gamma gene transfer results in decreased RSV replication and pulmonary inflammation and may be useful against RSV infection.

Administration, Intranasal↗

PubMed1999

The importance of the diluent for airway transport of toluene diisocyanate following intranasal dosing of mice.

Uncertainty of the transport of reactive chemicals to the lung is a major concern when using intranasal dosing of animals. In a preliminary study using mice, intranasal instillation of the dyes methylene blue (in water) and Sudan black B (in 1:4 ethyl acetate:olive oil), indicated that the following conditions were necessary to achieve transport to the lung: (1) aqueous diluent, (2) light anesthesia prior to dosing, (3) holding the animal in a supine position during chemical application, and (4) maintaining the animal in the same position postdosing. Using these conditions, we investigated the distribution of toluene diisocyanate (TDI), a major industrial asthmogen, to the lung following intranasal administration. Female C57BL/6 mice received 20 microl of 1% TDI in ethyl acetate:olive oil (1:4). Group 1 received a single application on day 1; group 2, single applications on 2 consecutive days; group 3, single applications on 4 consecutive days; and group 4, a single application of the vehicle on 2 consecutive days. All mice were necropsied 24 h after the final application. The nasal passages, upper pharynx, trachea, lungs, and olfactory bulbs of each animal were examined with hematoxylin-eosin and immunohistochemical staining, the latter using a rabbit anti-TDI antiserum. Histopathology revealed desquamation of ciliated epithelial cells as well as inflammatory cell debris in the nasal cavity and upper pharynx of animals in groups 1-3. The intensity of these changes was dependent on the number of applications. No inflammation was observed in the trachea, lungs, or olfactory bulbs in any of the groups. Immunohistochemical examination revealed positive staining for the TDI moiety in epithelial cells of the nasal cavity and upper pharynx in animals of groups 1-3. No staining was observed in the trachea, lungs, or olfactory bulbs of any animal. These results suggest that TDI, when dissolved in olive oil:ethyl acetate and applied intranasally, does not reach the trachea and/or lower airways.

Administration, Intranasal↗

PubMed2003

Identification of the domains of the fibronectin-binding protein I of Streptococcus pyogenes responsible for adjuvanticity.

Intranasal administration of antigens coupled to full-length fibronectin-binding protein I (SfbI) of Streptococcus pyogenes results in the elicitation of improved humoral and cellular immune responses, at both systemic and mucosal levels. We want to evaluate if SfbI also exhibits adjuvant properties when co-administered with the antigen, as well as identify the minimal domain responsible for its adjuvanticity. To achieve this aim, mice were immunized by the intranasal route with the model antigen beta-galactosidase (beta-gal) co-administered with recombinant proteins spanning different portions of the SfbI protein. The obtained results demonstrated that the adjuvant properties of SfbI were maintained intact when admixed to the model antigen. Similar kinetics and absolute titers of beta-gal-specific IgG antibodies as well as a dominant IgG(1) isotype response pattern were observed using SfbI derivatives spanning either the aromatic and proline-rich (H10) or the fibronectin-binding (H12) domains, respectively. The use of all tested derivatives also stimulated the elicitation of efficient beta-gal-specific IgA responses in lung lavages (23-25% of the total IgA). The obtained results suggest that different sub-domains of the SfbI protein can be used as adjuvants for the development of mucosal vaccines.

Adhesins, Bacterial↗

PubMed2006

Immunological evaluation of bacterial derived Cochleate and proteoliposome as mucosal adjuvants.

We evaluated the potential of two bacterial derived compounds, Cochleate and Proteoliposome (PL), administrated to mice by nasal or oral routes on induction of antibody and cytokine responses. Anti PL IgG and IgA responses were measured by ELISA in saliva, sera or vaginal fluids of immunized mice. Productions of gammaIFN and IL-5 were determined in spleen cells of immunized mice following a recall in vitro with Cochleate or PL. Intranasal administration elicited a higher anti PL IgA response in both saliva and vaginal fluids as compared with oral route. Mice immunized with Cochleate or PL via intranasal or oral route-induced anti PL IgG and IgG2a antibody responses in their sera and vaginal fluids. Spleen cells from these immunized mice produced gammaIFN, but not IL-5, after a recall in vitro with Cochleate or PL. These results show that Cochleate and PL are capable of inducing both systemic and mucosal antibody responses as well as a Th1 type of immunity as evidenced by high gammaIFN and IgG2a antibody responses.

Adjuvants, Immunologic↗

PubMed2001

A novel bioadhesive intranasal delivery system for inactivated influenza vaccines.

The aim of the current studies was to evaluate a bioadhesive delivery system for intranasal administration of a flu vaccine, in combination with a mucosal adjuvant (LTK63). A commercially available influenza vaccine, containing hemagglutinin (HA) from influenza/A Johannesberg H1N1 1996, and LTK63 or LTR72 adjuvants, which are genetically detoxified derivatives of heat labile enterotoxin from Escherichia coli, were administered IN in a bioadhesive delivery system, which comprised esterified hyaluronic acid (HYAFF) microspheres, to mice, rabbits and micro-pigs at days 0 and 28. For comparison, additional groups of animals were immunized intranasally with the HA vaccine alone, with soluble HA+LTK63, or IM with HA. In all three species, the groups of animals receiving IN immunization with the bioadhesive microsphere formulations, including LT mutants, showed significantly enhanced serum IgG responses (P<0.05) and higher hemagglutination inhibition (HI) titers in comparison to the other groups. In addition, the bioadhesive formulation also showed a significantly enhanced nasal wash IgA response (P<0.05). Most encouragingly, in pigs, the bioadhesive microsphere vaccine delivery system induced serum immune responses following IN immunization, which were significantly more potent than those induced by traditional IM immunization at the same vaccine dose (P<0.05).

Administration, Intranasal↗

PubMed1981

[Feline rhinotracheitis in stray cats; to vaccinate or not to vaccinate?].

Report on a controlled field trial in an animal home housing both stray cats and animals which were boarders. In this home, a vaccine containing live attenuated feline herpes and calici viruses for intranasal administration was inoculated. The purpose of the trial was to find out why this vaccine which had been very successful in this animal home during the past years, showed disappointing results in stray cats in recent months. The necessary practical measures were taken to ensure that the required procedure should be complied with, i.e., every stray cat was vaccinated on the day of admission and was then held in quarantine for at least 24 hours. In the first group of fifty stray cats, only some local reactions following vaccination were observed. When vaccination was discontinued, feline rhinotracheitis became enzootic in non-vaccinated cats within a month. A second group of forty-five stray cats was then vaccinated with equally satisfactory results. It was found that feline rhinotracheitis can be controlled in stray cats even under enzootic conditions by intranasal vaccination on the day of admission and then holding the cats for at least 24 hours in quarantine.

Administration, Intranasal↗

PubMed2005

Immune modulation of collagen-induced arthritis by intranasal cytokine gene delivery: a model for the therapy of rheumatoid arthritis.

OBJECTIVE: To develop a passively targeted, patient-compliant, intranasal interleukin-10 (IL-10) gene therapy delivery system and to investigate its therapeutic benefit in experimental collagen-induced arthritis, a model of rheumatoid arthritis. METHODS: Arthritis was induced in DBA/1 mice and monitored following intranasal administration of an IL-10 plasmid (pG-IL-10) or the empty vector 2 days (days -2 and 19) prior to collagen injection (prophylactic group, as a single dose after collagen boost on day 21 (early therapy group, or as a single dose upon acquisition of a disease score of 3 (late therapy group. IL-10-induced alterations in cytokine secretion and proliferation by spleen and lymph node cells were assessed on days 31 and 65 and correlated with histologic changes and bone erosions assessed on day 65. RESULTS: Intranasal delivery of pG-IL-10 significantly delayed arthritis onset and reduced disease severity in the prophylactic group and early therapy group, reduced cellular infiltration and bone loss in the early therapy group, and reduced T cell proliferation in response to collagen on days 31 and 65 in these two groups, with a significant reduction in tumor necrosis factor alpha production on day 65. Within the late therapy group, disease progression was arrested for the rest of the study. The intranasally administered pG-IL-10 targeted monocytes and macrophages and showed dissemination to inflamed joints and draining lymph nodes in vivo. Importantly, systemic levels of IL-10 (in serum) were transient (peaking on day 2) and undetectable by day 4. CONCLUSION: Intranasal IL-10 gene delivery significantly reduces bone destruction, shows evidence of reducing joint inflammation, and may be mediated by high local levels of IL-10 produced by transfected monocytes trafficking to inflamed joints and draining lymph nodes.

Administration, Intranasal↗

PubMed1999

Intranasal exposure to protein antigen induces immunological tolerance mediated by functionally disabled CD4+ T cells.

In this study we examined the immunological parameters underlying the natural immunity to inhaled nonpathogenic proteins. We addressed this question by examining the effect of intranasal exposure to OVA in both wild-type mice and mice reconstituted with OVA-TCR transgenic CD4+ T cells. Intranasal administration of OVA induced an initial phase of activation during which CD4+ T cells were capable of proliferating and producing cytokines. Although many of the OVA-specific CD4+ T cells were subsequently depleted from the lymphoid organs, a stable population of such T cells survived but remained refractory to antigenic rechallenge. The unresponsive state was not associated with immune deviation due to selective secretion of Th1- or Th2-type cytokines, and the presence of regulatory CD8+ T cells was not required. Moreover, neutralization of the immunosuppressive cytokines IL-10 and TGF-beta did not abrogate the induction of tolerance. Inhibition of the interaction of T cells with CD86, but not CD80, at the time of exposure to intranasal Ag prevented the development of unresponsiveness, while selective blockade of CTLA-4 had no effect. Our results suggest that intranasal exposure to Ags results in immunological tolerance mediated by functionally impaired CD4+ T cells via a costimulatory pathway that requires CD86.

Abatacept↗

PubMed1981

[Characterization of FVIII/VW circulating after DDAVP administration (author's transl)].

These studies were designed with the purpose of providing more information relevant about the new FVIII/VW circulating after administration intranasally DDAVP. One health subject was administered 260 microliter total dose of DDAVP. The newly released FVIII/VW could not be distinguished form circulating FVIII/VW on the basis of molecular size, electrophoretic mobility or "in vitro" stability of VIII:C and VIIIR:AG despite apparent differences in the duration of response of the procoagulant and antigenic components "in vivo". FVIII/VW cryoethanol-precipitations studies showed similar increase in the high molecular weight (HMW) and low molecular weight (LMW) after DDAVP administration. This suggest a immediately polymerization in the new VIIIR:AG circulating after DDAVP administration.

Administration, Intranasal↗

PubMed2001

Evaluation of the adjuvant effect of Escherichia coli heat-labile enterotoxin mutant (LTK63) on the systemic immune responses to intranasally co-administered measles virus nucleoprotein. Part I: antibody responses.

The adjuvanticity and immunogenicity of the heat-labile enterotoxin (LT) of Escherichia coli and of its non-toxic mutant, LTK63, was evaluated after intranasal administration of CBA mice with recombinant measles virus nucleoprotein (rMVNP) with or without LT or LTK63. Both LT and LTK63 were shown to be highly immunogenic with higher responses observed 4 weeks after the booster immunization. Although the nucleoprotein was immunogenic on its own, mice immunized with the nucleoprotein plus wild type LT produced significantly high antibody responses (p< 0.01). Mice that received the rMVNP with LTK63 also generated strong antibody responses to rMVNP. These antibodies were also significantly higher than those of rMVNP alone (p< 0.05). No significant differences were observed between groups of mice immunized intranasally with rMVNP plus LT or LTK63 (p> 0.05). Data on IgG antibody isotype profiles showed that IgG 1 and IgG 2a were predominant in mice immunized with rMVNP + LT or LTK63 whereas IgG 1 predominated when rMVNP was given on its own implying that LT and LTK63 induce both Th1 and Th2-type immune responses. These results highlight the great potential of this non-toxic mutant of LT as a safe vaccine adjuvant.

Adjuvants, Immunologic↗

PubMed1996

Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes.

We previously demonstrated that a spontaneous Th1 response against glutamate decarboxylase (GAD65) arises in NOD mice at four weeks in age and subsequently T cell autoimmunity spreads both intramolecularly and intermolecularly. Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. We observed that a single intranasal administration of GAD65 peptides to 2-3-wk-old NOD mice induced high levels of IgG1 antibodies to GAD65. GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. This active mechanism not only inhibited the development of proliferative T cell responses to GAD65, it also limited the expansion of autoreactive T cell responses to other beta cell antigens (i.e., determinant spreading). Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. Collectively, these data suggest that the nasal administration of GAD65 peptides induces a Th2 cell response that inhibits the spontaneous development of autoreactive Th1 responses and the progression of beta cell autoimmunity in NOD mice.

Administration, Intranasal↗

PubMed1997

Effects of intranasal exposure to spores of Stachybotrys atra in mice.

The effects of highly toxic and nontoxic spores of Stachybotrys atra were investigated in mice after six intranasal administrations of 1 x 10(5) and 1 x 10(3) spores in phosphate-buffered saline during a 3-week period. Toxic spores contained the trichothecene mycotoxins, satratoxins G and H, as well as the immunosuppressant stachybotrylactones and -lactams. No trichothecenes were detected in the nontoxic spores, and they contained only minor amounts of stachybotrylactones and -lactams. In mice injected with toxic and nontoxic spores, the platelet count was decreased and leucocyte and erythrocyte counts, hemoglobin concentration, and hematocrit were increased. No IgG antibodies to S. atra were detected in sera of mice exposed intranasally to spores. No histological changes were detected in spleen, thymus, or intestines of mice. The mice receiving 1 x 10(5) toxic spores intranasally developed severe inflammatory changes within both bronchioles and alveoli. Hemorrhage was detected in alveoli. The mice receiving 1 x 10(5) nontoxic spores also developed inflammatory changes in the lungs, but these changes were significantly milder than those in mice receiving toxic spores. The mice receiving 1 x 10(3) toxic spores developed inflammatory changes in the lungs that were less severe than those in the mice receiving 1 x 10(5) toxic spores. No inflammatory changes were detected in the mice receiving 1 x 10(3) of nontoxic spores. The present findings indicate that exposure to S. atra spores containing toxins (satratoxins) can be a significant health risk.

Administration, Intranasal↗

PubMed2005

Distribution and phenotype of murine rotavirus-specific B cells induced by intranasal immunization with 2/6 virus-like particles.

Virus-like particles containing the rotavirus (RV) internal proteins VP2 and VP6 (2/6-VLP) have been shown to induce serum and fecal antibodies as well as protection in mice after intranasal administration with a mutant of E. coli toxin, LT-R192G. To better understand the origin of fecal IgA induced by this protocol, we studied the RV-specific B cell response in systemic and mucosal lymphoid tissues using a flow cytometry assay that allows quantification and phenotypic characterization of RV-specific B lymphocytes. We also assessed the RV-specific antibody-secreting cells in the spleen and intestinal lamina propria (ILP). A remarkably high frequency of RV-specific B cells was found in the respiratory lymphoid tissues and spleen, of which only a minority expressed the alpha4beta7 integrin (intestinal homing receptor). In contrast, but in accordance with alpha4beta7 expression at the induction site, a very low response was observed in intestinal lymphoid tissues (mesenteric lymph nodes and ILP), which did not increase after a second immunization. Thus, intranasal immunization with a nonreplicating antigen does not induce an important number of RV-specific B cells with an intestinal homing profile.

Administration, Intranasal↗

PubMed1985

Regional and systemic immune responses to trinitrophenyl derivatives after intranasal and subcutaneous sensitization of mice.

The immune responses and accompanying inflammatory local reactions were analyzed in mice sensitized subcutaneously (SC) or intranasally. Administration of picrylsulfonic acid (PSA) by both routes for two 2- or 1-week periods with a 4-week interval resulted in delayed hypersensitivity responses. Serum antibodies of the IgG and IgE and some of the IgA isotype were found, particularly in SC-sensitized animals. The latter animals also had levels of IgG antibodies in their bronchial fluid. Lymph node cells from mice sensitized for 2-week periods demonstrated high spontaneous proliferation. After culture together with spleen cells, these cells exhibited considerable numbers of mast cells, particularly after stimulation with pokeweed and antigen. The lungs from mice sensitized intranasally revealed increased numbers of mononuclear cells around large vessels and mucous cells in the bronchiolar epithelium, although there were individual differences between the animals. The mast cell numbers in the lungs were only slightly increased compared with numbers in nonimmunized animals subjected to ether anesthesia. Animals injected SC with PSA exhibited increased numbers of mast cells in their lungs compared with control mice. Mice sensitized with trinitrophenylated human serum albumin demonstrated some differences in their immune reactivity compared with animals immunized with PSA. Thus, no obvious delayed hypersensitivity appeared, but the IgG antibody titers were higher, and the IgE antibody titers were lower. The cellular responses assessed histologically demonstrated higher mononuclear cell numbers and lower mast cell numbers compared with those observed in animals sensitized with PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed2001

Inhibition of mucosal and systemic T(h)2-type immune responses by intranasal peptides containing a dominant T cell epitope of the allergen Der p 1.

Although the intranasal administration of peptides containing T cell epitopes has been shown to be a potent method of inhibiting responses to the allergen Der p 1, the experiments to date have concentrated on their ability to regulate immune responses to the injection of antigen in a T(h)1-type adjuvant. Their ability to regulate responses to a T(h)2-type immunization and to sensitization via the respiratory mucosa has not been examined. Here it is shown that peptide used in doses required to block delayed-type hypersensitivity can also readily inhibit IgE responses to Der p 1 injected in alum. To examine responses induced in the respiratory mucosa, mice pretreated with intranasal peptide were sensitized with an intranasal dose of Der p 1 in conjunction with a mutated enterotoxin adjuvant. Intranasal peptide even in very high doses did not reduce IgE titers, but the ability of cells from the draining lymph nodes to release IL-4 and IL-13 but not IL-2, IL-5, IL-10 or IFN-gamma was reduced. These are the first reports on the effect of intranasal peptides containing T cell epitopes on IgE in T(h)2 immunization and on responses to respiratory immunization. Thus the effect of the peptide-induced mucosal tolerance differs depending on the type of immunization used for sensitization, but the potential to inhibit T(h)2 responses and responses to respiratory sensitization as well as T(h)1 responses has been demonstrated.

Administration, Intranasal↗

PubMed1999

Mucosal immunogenicity and adjuvant activity of the recombinant A subunit of the Escherichia coli heat-labile enterotoxin.

The Escherichia coli heat-labile enterotoxin (LT) is an exceptionally effective mucosal immunogen and mucosal immunoadjuvant towards coadministered antigens. Although, in general, the molecular basis of these properties is poorly understood, both the toxic ADP-ribosylation activity of the LTA subunit and the cellular toxin receptor, ganglioside, GM1-binding properties of the LTB-pentamer have been suggested to be involved. In recent studies we found that GM1-binding is not essential for the adjuvanticity of LT, suggesting an important role for the LTA subunit in immune stimulation. We now describe the immunomodulatory properties of recombinant LTA molecules with or without ADP-ribosylation activity, LTA(His)10 and LTA-E112K(His)10, respectively. These molecules were expressed as fusion proteins with an N-terminal His-tag to allow simple purification on nickel-chelate columns. Their immunogenic and immunoadjuvant properties were assessed upon intranasal administration to mice, and antigen-specific serum immunoglobulin-isotype and -subtype responses and mucosal secretory immunoglobulin A (IgA) responses were monitored using enzyme-linked immunosorbent assay. With respect to immunogenicity, both LTA(His)10 and LTA-E112K(His)10 failed to induce antibody responses. On the other hand, immunization with both LT and the non-toxic LT-E112K mutant not only induced brisk LTB-specific, but also LTA-specific serum and mucosal antibody responses. Therefore, we conclude that linkage of LTA to the LTB pentamer is essential for the induction of LTA-specific responses. With respect to adjuvanticity, both LTA(His)10 and LTA-E112K(His)10 were found to stimulate serum and mucosal antibody responses towards coadministered influenza subunit antigen. Remarkably, responses obtained with LTA(His)10 were comparable in both magnitude and serum immunoglobulin isotype and subtype distributions to those observed after coimmunization with LT, LT-E112K, or recombinant LTB. We conclude that LTA, by itself, can act as a potent adjuvant for intranasally administered antigens in a fashion independent of ADP-ribosylation activity and association with the LTB pentamer.

Adjuvants, Immunologic↗

PubMed1993

Intranasal calcitonin suppresses increased bone resorption during short-term immobilization: a double-blind study of the effects of intranasal calcitonin on biochemical parameters of bone turnover.

Immobilization is associated with increased bone resorption and decreased bone formation. We evaluated in a double-blind trial the effect of intranasal administration of salmon calcitonin on biochemical parameters of bone turnover in 32 patients immobilized for a prolapsed intervertebral disk. Calcitonin in a dose of two times 200 IU/day partially inhibited the increase in the fasting 2 h urinary hydroxyproline/creatinine ratio (OHPr/Cr) and calcium/creatinine ratio (Ca/Cr). The increase in OHPr/Cr was 40% less in the calcitonin group compared to the placebo group (P = 0.01), and the increase in Ca/Cr was 80% less in the calcitonin group (P = 0.04). Calcitonin also partially inhibited the increase in serum cross-linked carboxyl-terminal telopeptide of collagen type I (P < 0.05). The decrease in serum 1,25-dihydroxyvitamin D after 10 days of immobilization was significantly less in the calcitonin-treated group than in the placebo group (14 versus 29%, respectively; P < 0.05). Intranasal calcitonin did not influence the pain scores as measured with a visual analog scale (VAS). The tolerability of the nasal calcitonin preparation was excellent. We conclude that nasal salmon calcitonin counteracts the early increase in bone resorption induced by immobilization.

Administration, Intranasal↗