JP4463525B2 - Desensitization therapy agent - Google Patents

Description

  The present invention relates to an agent for desensitization therapy using bifidobacteria.

Immunity is a biological defense system that excludes foreign substances such as viruses and pathogenic bacteria, and animals survive without being affected by various foreign substances. However, it is called allergy when the immunity originally intended to protect the body harms the living body. Abnormal immunity reacts with what is generally considered harmless, such as dust, mites, pollen or food in the air, and hay fever, asthma, atopic dermatitis, etc. develop. For example, when pollen enters the body (nose), it is regarded as a foreign substance (so-called antigen), antigen-presenting cells and T lymphocytes work, and finally B lymphocytes have antibodies (Ig; immunity) against this pollen antigen. Globulin). The antibody types are IgG, IgA, and IgM, which are known to occupy most of the antibody. These antibodies are important antibodies related to infection and biological defense, but they may produce an antibody called IgE in which B lymphocytes cause allergy against pollen that has entered the nose due to various factors. . When this IgE binds to the surface of mast cells (the state where mast cells are sensitized to pollen antigen: also referred to as sensitized mast cells), when pollen enters the nose again in this state, the feeling in the nasal tissue Pollen antigen and IgE bind on the cultured mast cells, and the mast cells release chemical mediators such as histamine and leukotriene to the outside of the cells and induce inflammation in blood vessels and other tissues. This inflammation will cause nasal inflammation symptoms such as sneezing, runny nose and nasal congestion.
Allergic diseases such as hay fever, asthma, and atopic dermatitis continue to increase and are said to be national illnesses. In addition to genetic factors (allergy family calendar), environmental factors and changes in dietary habits are also intertwined and low. It is said that aging and difficult treatment are progressing.

  Currently, allergic diseases are symptomatic, i.e. alleviating allergic symptoms. Various drugs have been used, and it has become possible to control allergic diseases to some extent. However, these are only symptomatic treatments, not radical treatments that cure allergic diseases themselves. For this reason, in the case of hay fever, it is necessary to continue to use the drug every year during the pollen dispersal period, and taking into account the aging of allergic onset, it may result in extremely long-term drug therapy. For this reason, radical treatment is desired. As described above, IgE is deeply involved in the development of allergy, and as a radical treatment method for allergic diseases described above, it is necessary not to produce IgE or to suppress its action.

Currently, there is desensitization therapy as a radical treatment for allergic diseases. There are two types of desensitization therapy: antigen-specific desensitization therapy and non-specific desensitization therapy. In specific desensitization therapy, a minute amount of allergen (antigen) or a part of an antigen that does not cause allergy is injected, and a living body that can tolerate the antigen is modulated. More specifically, for example, specific desensitization therapy for hay fever will be described. When the causative substance (pollen) enters the body, the production of antigen-specific IgE is reduced and the binding of antigen-specific IgE to immune cells is blocked. Production of antibodies, decreased mast cell responsiveness to specific antigens, decreased Th2 cytokine production, and increased local Th1 type cytokines. However, the fundamental action reaction site and mechanism are unknown, and it is said that some kind of immune tolerance is involved.
On the other hand, non-specific desensitization therapy is considered to be effective desensitization therapy when no antigen is specified or when sensitized to multiple antigens. Histoglobulin and gold preparations have been used for a long time, but allergic diseases are a state in which the response of Th2 cells is abnormally enhanced among helper T lymphocytes. In recent years, treatments have been attempted to adjust the balance (generally referred to as Th1 / Th2 balance) by enhancing the response of the related Th1 cells. For example, treatment by administering BCG that strongly induces a Th1-type reaction or Th1 cytokines such as interferon γ and interleukin 12 has been attempted (it is considered to be less preferable because of problems such as side effects). On the other hand, non-antigen-specific humanized anti-IgE (omalizumab) has been shown to have some effect by reducing non-specific IgE.

In recent years, a group of Finnish doctors administered lactic acid bacteria to a pregnant woman who had a genetically allergic disease, and also administered lactic acid bacteria to a baby who gave birth, and the incidence of allergic disease in the infant was reduced by about 50%. (See Non-Patent Document 1).
In addition, when examining the fecal flora of infants and children with allergic diseases, it has been reported that lactic acid bacteria such as bifidobacteria have decreased, and the relationship of lactic acid bacteria to the development of allergic diseases has been pointed out (non- (See Patent Document 2).

There are also reports on the relationship between allergies and bacteria belonging to the genus Bifidobacterium. For example, Bifidobacterium infantis and Bifidobacterium breve suppress IgE and IgG production and thus are antiallergic agents. And it is described that it is useful as a fermented food (refer patent document 1).
Enterococcus faecalis and Lactobacillus reuteri have an inhibitory effect on histamine release, an inhibitory effect on the PCA reaction, and also suppressed inflammation in a contact dermatitis reaction, which is a delayed hypersensitivity reaction. It is described that it is useful for type allergy (see Patent Document 2).
It has also been reported that oral administration of a combination of Bifidobacteria with Acidophilus bacteria is useful in the prevention and improvement treatment of allergies (see Patent Document 3).
However, for the lactic acid bacteria, there is no description that selectively inhibits IgE production without inhibiting IgG production.
JP-A-10-309178 JP 2000-95697 A JP 2000-86524 A Karliomaki M and five others, Lancet April 2001, 7; 357 (9262), p. 1076-1079 Owehand AC and 4 others, The Journal of Allergy and Clinical Immunology, July 2001, Vol. 108 (1), p. 144-145

  An object of the present invention is to provide an agent for desensitization therapy for allergy, particularly a non-specific desensitization therapy agent.

  In order to achieve the above object, the present inventors screened several tens of lactic acid strains using the action on immune cells as an index. That is, a lactic acid strain having an action of tilting the balance of helper T cells to Th1 type was screened by a conventional screening method using Th1 / Th2 balance as an index. As a result, Enterococcus faecalis, which is thought to be strongly stimulated to Th1 cells, was obtained. On the other hand, unlike Enterococcus faecalis, certain strains belonging to the genus Bifidobacterium that were very weakly stimulated by Th1 cells were also very interesting. Therefore, when the influence of these two strains on the IgE and IgG production of animals was examined, it was found that certain strains belonging to the genus Bifidobacterium suppress IgE production without suppressing the production of IgG involved in infection protection. I got the knowledge. As a result of further research, the present inventors have found that certain strains belonging to the genus Bifidobacterium selectively suppress IgE production without suppressing IgG production even by oral administration. As a result, it was found that there is an action to suppress allergic phenomena regardless of the type of allergen. Since this bacterium belongs to the genus Bifidobacterium, it is considered to be a very safe bacterium and can be ingested not only as a medicine but also as a food on a daily basis. The present invention has been completed based on these findings.

That is, the present invention
(1) A desensitizing therapeutic agent for allergic diseases, comprising a bacterium belonging to the genus Bifidobacterium that selectively suppresses the production of IgE without suppressing the production of IgG,
(2) The agent for desensitization therapy according to (1) above, wherein the bacterium belonging to the genus Bifidobacterium is Bifidobacterium bifidum,
(3) The agent for desensitization therapy according to (2) above, wherein the Bifidobacterium bifidum is Bifidobacterium bifidum G9-1,
(4) The agent for desensitization therapy according to (1) or (2) above, wherein the desensitization therapy is nonspecific desensitization therapy, and (5) allergic rhinitis, hay fever, bronchial disease The agent for desensitization therapy according to any one of the above (1) to (4), which is a disease selected from asthma, allergic dermatitis, urticaria, atopic dermatitis and food allergy,
About.

Since the agent for desensitization therapy of the present invention does not suppress IgG production, even when the agent for desensitization therapy of the present invention is ingested, IgG does not decrease and IgE production can be selectively suppressed. . Therefore, by continuing to take the agent for desensitization therapy of the present invention, patients with a history of allergies will be placed in a desensitization state, hay fever that develops due to the invasion of antigens such as cedar pollen, and Can suppress the onset of allergic rhinitis, bronchial asthma, allergic dermatitis (including contact dermatitis), urticaria, atopic dermatitis and food allergy.
Moreover, the agent for desensitization therapy of this invention is useful also for the desensitization of the allergic patient who cannot identify an allergen. Therefore, it can be taken for the prevention and treatment of allergic diseases based on various allergens.
In addition, allergic reactions to new allergens can be prevented. The agent for desensitization therapy of the present invention is safe and has no side effects, and can be safely ingested for a long period of time for the purpose of maintaining and improving health.

  The above “selectively suppress the production of IgE without suppressing the production of IgG” does not inhibit the production of IgG in the living body and affects the production ratio of IgG subclasses, particularly the production ratio of IgG1 and IgG2a. This refers to selectively suppressing the production of IgE without giving it, but it is not limited to selectively suppressing the production of IgE, and cells (particularly mast cells) are bound to IgE on the cell surface, that is, sensitized. It is also included to suppress this.

  As the bacterium belonging to the genus Bifidobacterium used in the present invention, Bifidobacterium bifidum is preferable, and Bifidobacterium bifidum G9-1 strain is particularly preferable. These cells can be easily obtained from, for example, an organization such as ATCC or IFO or the Japan Bifidobacteria Center. Moreover, what is marketed can also be used suitably.

  In addition, the bacteria belonging to the genus Bifidobacterium used in the present invention include processed products of these bacteria as long as they do not lose their IgE production inhibitory activity. The treated product of these bacteria refers to a product obtained by adding some treatment to a bacterium belonging to the genus Bifidobacterium, and the treatment is not particularly limited. Specific examples of the treated product include a disruption solution of the microbial cells by ultrasonic waves, a culture solution or culture supernatant of the microbial cells, and a solid residue obtained by separating them by solid-liquid separation means such as filtration or centrifugation. It is done. In addition, treatment solutions obtained by removing cell walls with enzymes or mechanical means, protein complexes (proteins, lipoproteins, glycoproteins, etc.) and peptide complexes (peptides, glycopeptides, etc.) obtained by trichloroacetic acid treatment or salting out treatment, etc. ) Etc. are also mentioned as the treated product. Furthermore, these concentrates, these dilutions, or these dried products are also included in the treated product. In addition, the treated product in the present invention includes those obtained by further adding, for example, various chromatographic separations to the disruption solution of the bacterial cells by ultrasonic waves, the culture solution or culture supernatant of the cells, and the like. . Bacteria belonging to the genus Bifidobacterium include not only living cells but also dead cells in the treated product of the present invention. The dead cells can be obtained by, for example, enzyme treatment, heat treatment at about 100 ° C., treatment with drugs such as antibiotics, treatment with chemicals such as formalin, treatment with radiation such as γ rays. it can. Since the processing method has been well established in the past, it may be followed in the present invention.

  The content of the bacterium belonging to the genus Bifidobacterium contained in the agent for desensitization therapy of the present invention varies depending on the type of bacteria and the method of treatment, and cannot be generally stated. For example, for example, the genus Bifidobacterium When the bacterium belonging to is Bifidobacterium bifidum G9-1, the agent for desensitization therapy according to the present invention preferably contains about 0.01 mg to 10 g / day of the bacterium.

  The agent for desensitization therapy according to the present invention can be used as a medicine. When used as a medicine, a bacterium belonging to the genus Bifidobacterium may be administered as it is, but in general, in the form of a pharmaceutical composition containing a bacterium belonging to the genus Bifidobacterium and a pharmaceutical additive. It is desirable to administer. The pharmaceutical composition may take the form of oral solid preparations such as capsules, tablets (including coated tablets such as sugar-coated tablets or enteric tablets or multilayer tablets), powders or granules, orally. It may take the form of a liquid preparation, or may take the form of a parenteral preparation such as an injection, infusion, suppository, spray, or external preparation. These preparations can be produced according to known methods.

Specifically, for the production of liquid preparations suitable for oral administration, for example, sugars such as sucrose, sorbit and fructose; glycols such as polyethylene glycol and propylene glycol; oils such as sesame oil, olive oil and soybean oil; -Preservatives such as hydroxybenzoic acid esters can be used. As the solvent or dispersion medium, for example, a known orally administrable medium such as water or alcohol, or a mixture thereof is used.
For the production of oral solid preparations such as capsules, tablets, powders or granules, for example, excipients such as lactose, glucose, sucrose and mannitol; disintegrants such as starch and sodium alginate; magnesium stearate Lubricants such as talc, binders such as polyvinyl alcohol, hydroxypropyl cellulose, and gelatin; surfactants such as fatty acid esters; plasticizers such as glycerin, and the like can be used.

Among preparations suitable for parenteral administration, preparations for intravascular administration such as injections and infusions can be prepared preferably using an aqueous medium isotonic with body fluids. For example, the injection is prepared as a solution, suspension or dispersion together with an appropriate auxiliary agent using an aqueous medium selected from distilled water for injection, salt solution, glucose solution or a mixture of salt solution and glucose solution, according to a conventional method. can do. Suppositories for enteral administration can be prepared using carriers such as cocoa butter, hydrogenated fat or hydrogenated carboxylic acid. The propellant can be prepared using a carrier that does not irritate the oral cavity and airway mucosa and can promote absorption by dispersing the active ingredient of the medicament of the present invention as fine particles. As such a carrier, for example, lactose or glycerin can be used. In addition, it can also be prepared in the form of aerosol, dry powder and the like.
For the production of a parenteral preparation as described above, for example, 1 selected from diluents, fragrances, preservatives, excipients, disintegrants, lubricants, binders, surfactants, plasticizers, etc. Two or more pharmaceutical additives can be used.
Moreover, the agent for desensitization therapy of this invention can also contain another medicinal component, unless it is contrary to the objective of this invention.

  The administration route, dosage amount, and administration frequency of the agent for desensitization therapy of the present invention are not particularly limited, and can be appropriately selected according to various conditions such as patient age, body weight, and symptoms. Of these, oral administration is preferable as the administration route. In addition, for example, in the case of oral administration, the dose of the medicament according to the present invention may be selected so that the dose of a bacterium belonging to the genus Bifidobacterium is about 0.01 mg to 10 g per adult day. preferable. In addition, when the medicament according to the present invention is administered intradermally or subcutaneously, it is preferable to select so that the bacteria belonging to the genus Bifidobacterium are about 0.01 μg to 10 mg. However, the dose is not limited to these.

The agent for desensitization therapy according to the present invention may be used not only as a medicine but also as a food or drink such as a nutritive food, functional food, food for specified health use, infant formula or a drink. When used as food, it can be provided in the form of granules, tablet confectionery, gum, candy, jelly or beverage. When the agent for desensitization therapy according to the present invention is used as food, the content of bacteria belonging to the genus Bifidobacterium can be appropriately selected according to the form of the food. When the food according to the present invention is, for example, a food containing Bifidobacterium bifidum G9-1, the number of Bifidobacterium bifidum G9-1 is about 1.0 × 10 ⁵ cells / g or more, preferably It is preferable that about 1.0 * 10 < ⁶ > -1.0 * 10 < ¹² > piece / g is contained.

  The agent for desensitization therapy according to the present invention includes not only humans but also mammals other than humans (for example, domestic animals such as cows, horses, pigs, sheep or goats, pet animals such as dogs and cats, other mice, rats, It can also be applied to rabbits, monkeys, etc.). That is, the agent for desensitization therapy according to the present invention can be used as an animal drug or can be used by mixing with feed or the like.

Hereinafter, the present invention will be described using experimental examples and formulation examples, but the present invention is not limited thereto.
In addition, the meaning of each abbreviation used in an Example is as follows.
EF-JCM: Enterococcus faecalis JCM8726 strain BBG9-1: Bifidobacterium bifidum G9-1 strain OVA: Ovalbumin IL-12: Interleukin-12
IFN-γ: Interferon gamma VF: Liquid medium for Bifidobacterium test (1) (Japanese Pharmacopoeia Pharmaceutical Standards)
2-ME: 2-mercaptoethanol PBS: phosphate buffered saline RPMI 1640: RPMI-1640 medium FCS: fetal calf serum BSA: bovine serum albumin HRP: horseradish peroxidase (horseradish peroxidase)
ELISA: enzyme immunoassay TMB: 3,3′5,5′-tetramethylbenzidine PCA: passively sensitized skin anaphylaxis Unless otherwise specified,% is mass%.

  After the BBG9-1 cryopreserved strain was statically cultured at 37 ° C. for 24 hours, this cultured bacterial solution was inoculated into VF at a ratio (volume ratio) of 1 to VF100, and statically cultured at 37 ° C. for 18 hours. The cultured bacterial solution is centrifuged (2500 rpm x 20 minutes), and the obtained bacterial cells are washed three times with purified water, and then an appropriate amount of purified water is added and heat-treated in a boiling water bath for 10 minutes to prepare dead cells. did. This solution was washed twice with purified water and then lyophilized. The obtained dried cells were resuspended at various concentrations using RPMI 1640 (containing 10% FCS, 55 μM 2-ME and 100 U / mL penicillin-streptomycin) to obtain sample solution A.

  The cryopreserved strain of EF-JCM was statically cultured at 37 ° C. for 24 hours, and then this cultured bacterial solution was inoculated into VF at a ratio (volume ratio) of 1 to VF100, and statically cultured at 37 ° C. for 18 hours. Subsequently, dry cells were obtained by the same method as described above. The obtained dried cells were resuspended at various concentrations using the above RPMI 1640 to obtain sample solution B.

The animals were immunized using 4-week-old BALB / c male mice with 1 μg of OVA and 2 mg of Al (OH) ₃ administered intraperitoneally, and after 1 week, the same method was applied. Next immunization. Two weeks after the second immunization, the mice were exsanguinated from the carotid artery under ether anesthesia and the spleen was removed. The spleen cells were extruded while lightly pressing the removed spleen with rubbed glass, filtered through a nylon mesh (200 mesh), and then centrifuged. To the obtained cells, hemolyzed blood (0.747 g ammonium chloride, 0.206 g trisaminomethane, 100 mL distilled water, pH 7.4) was added and hemolyzed in ice for 2 minutes. After washing with Hanks solution three times, RPMI 1640 (containing 10% FCS, 55 μM 2-ME and 100 U / mL penicillin-streptomycin) was added to prepare a cell suspension to 8 × 10 ⁶ cells / mL. 100 μL of this cell suspension and 100 μL of sample solution A or sample solution B were mixed in a 96-well microplate, and the IL-12 production amount after 24 hours of culturing at 37 ° C. in the presence of 5% CO ₂ and the IFN-γ production after 72 hours of culturing. The amount was measured. IL-12 was measured using Mouse Total IL-12 ELISA Kit (ENDOGEN), and IFN-γ was measured using Mouse IFN-γ immunoassay kit (R & D system).

  The results are shown in FIGS. EF-JCM was found to enhance IL-12 and IFN-γ production in a concentration-dependent manner, whereas BBG9-1 was found to have little effect on these productions.

Animals were immunized as in Example 1. There were three experimental groups: a BBG9-1 administration group, an EF-JCM administration group, and a control group, and the number of animals in each group was eight.
Moreover, preparation of BBG9-1 bacterial solution and EF-JCM bacterial solution was performed as follows. That is, after cryopreserving BBG9-1 and EF-JCM cryopreserved strains at 37 ° C. for 24 hours, this culture solution was inoculated into VF at a ratio (volume ratio) of 1 to VF100, and 18% at 37 ° C. The culture was allowed to stand for an hour. The obtained cultured bacterial solution is centrifuged, washed 3 times with physiological saline, and then suspended in physiological saline so that the number of surviving bacteria in the solution is 5 × 10 ¹⁰ per mL. Or EF-JCM bacterial solution.
Each bacterial solution obtained above was orally administered by gavage once a day for 14 days from one week before the first immunization to the second immunization. The administration liquid volume was 0.2 mL / animal. In the control group, the same amount of physiological saline was orally administered in the same schedule instead of the bacterial solution. Blood was collected from the carotid artery 3 weeks after the completion of secondary immunization, and serum was collected from the obtained blood by centrifugation. The total IgE in the serum was measured with a mouse IgE measurement kit (Morinaga Biochemical Laboratory). Moreover, the measurement of OVA specific IgE and IgG was performed as follows.

(Measurement of OVA-specific IgE)
100 μL of OVA prepared to 100 μg / mL was added to a 96-well immunoplate, and left overnight at 4 ° C. to immobilize OVA. Each well was washed three times with PBS containing 0.05% Tween 20 (hereinafter referred to as a washing solution), 200 μL of PBS containing 1% BSA was added, and the mixture was allowed to stand at 37 ° C. for 1 hour. Each well was washed 3 times with a washing solution, and then 50 μL of serum was added and stirred, and then left at 37 ° C. for 1 hour. Each well was washed four times with a washing solution, and then 100 μL of 1 μg / mL biotin-labeled rat anti-mouse IgE was added and left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of avidin-HRP diluted 1000 times was added and left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of TMB Microwell Peroxidase Substrate System was added and left at room temperature for 30 minutes. The reaction was stopped by adding 100 μL of 1N sulfuric acid solution, and the absorbance at 450 nm was measured to determine the amount of OVA-specific IgE.

(Measurement of OVA-specific IgG)
100 μL of OVA prepared to 100 μg / mL was added to a 96-well immunoplate, and left overnight at 4 ° C. to immobilize OVA. Each well was washed three times with the washing solution, 200 μL of PBS containing 1% BSA was added, and the mixture was allowed to stand at 37 ° C. for 1 hour. Each well was washed 3 times with a washing solution, and then 50 μL of serum was added and stirred, and then left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of 500-fold diluted HRP-labeled rat anti-mouse IgG was added and left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of TMB Microwell Peroxidase Substrate System was added and left at room temperature for 30 minutes. The reaction was stopped by adding 100 μL of 1N sulfuric acid solution, and the absorbance at 450 nm was measured to determine the amount of OVA-specific IgG.

  The results are shown in FIGS. EF-JCM tended to suppress IgE production, whereas BBG9-1 was found to significantly suppress IgE production. EF-JCM suppresses both OVA-specific IgE production and OVA-specific IgG production, whereas BBG9-1 selectively suppresses OVA-specific IgE production without suppressing OVA-specific IgG production. It turned out to be suppressed.

  Immunization to animals, sample administration, and serum collection were performed in the same manner as in Example 2. Measurement of OVA-specific IgG1 and measurement of OVA-specific IgG2a were performed as follows.

(Measurement of OVA-specific IgG1)
100 μL of OVA prepared to 100 μg / mL was added to a 96-well immunoplate, and left overnight at 4 ° C. to immobilize OVA. Each well was washed three times with the washing solution, 200 μL of PBS containing 1% BSA was added, and the mixture was allowed to stand at 37 ° C. for 1 hour. Each well was washed 3 times with a washing solution, and then 50 μL of serum was added and stirred, and then left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of 500-fold diluted HRP-labeled rat anti-mouse IgG1 was added and left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of TMB Microwell Peroxidase Substrate System was added and left at room temperature for 30 minutes. The reaction was stopped by adding 100 μL of a 1N sulfuric acid solution, and the absorbance at 450 nm was measured to determine the amount of OVA-specific IgG1.

(Measurement of OVA-specific IgG2a)
100 μL of OVA prepared to 100 μg / mL was added to a 96-well immunoplate, and left overnight at 4 ° C. to immobilize OVA. Each well was washed three times with the washing solution, 200 μL of PBS containing 1% BSA was added, and the mixture was allowed to stand at 37 ° C. for 1 hour. Each well was washed 3 times with a washing solution, and then 50 μL of serum was added and stirred, and then left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of HRP-labeled goat anti-mouse IgG2a diluted 50000 times was added and left at 37 ° C. for 1 hour. Each well was washed 4 times with a washing solution, and then 100 μL of TMB Microwell Peroxidase Substrate System was added and left at room temperature for 30 minutes. The reaction was stopped by adding 100 μL of 1N sulfuric acid solution, and the absorbance at 450 nm was measured to determine the amount of OVA-specific IgG2a. The amount of OVA-specific IgG1 obtained was divided by the amount of OVA-specific IgG2a to obtain an OVA-specific IgG1 / IgG2a ratio.

The results are shown in Table 1. EF-JCM decreased the OVA-specific IgG1 / IgG2a ratio, whereas BBG9-1 was found not to affect the OVA-specific IgG1 / IgG2a ratio.

  It was found that the agent for desensitization therapy of the present invention suppresses IgE production without suppressing IgG production.

  Since the agent for desensitization therapy of the present invention does not suppress IgG production, even when the agent for desensitization therapy of the present invention is ingested, IgG does not decrease and IgE production can be selectively suppressed. So, by taking safely over a long period of time, patients with a history of allergies can be put into a desensitized state, which is useful not only for patients who can identify allergens but also for allergic patients who cannot identify allergens. It is.

The production amount of interleukin 12 (IL-12) measured in Example 1 is shown. The production amount of interferon-γ (IFN-γ) measured in Example 1 is shown. The total amount of IgE in mouse serum measured in Example 2 is shown. In the figure, ** indicates a significant difference (p> 0.01) with respect to the control. The amount of OVA specific IgE in mouse serum measured in Example 2 is shown. In the figure, * indicates a significant difference (p> 0.05) relative to the control. The amount of OVA specific IgG in mouse serum measured in Example 2 is shown.

Claims (3)

An agent for desensitization therapy for allergic diseases, comprising Bifidobacterium bifidum G9-1 strain that selectively suppresses IgE production without suppressing IgG production. The agent for desensitization therapy according to claim 1 , wherein the desensitization therapy is nonspecific desensitization therapy. The agent for desensitization therapy according to claim 1 or 2 , wherein the allergic disease is a disease selected from allergic rhinitis, hay fever, bronchial asthma, allergic dermatitis, urticaria, atopic dermatitis and food allergy.

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