JP2020105158A - Immunomodulator - Google Patents
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Description
本発明は、免疫調整剤及びその製造方法等に関する。 The present invention relates to an immunomodulator, a method for producing the same, and the like.
高齢化の進展に伴って健康に対する意識がますます高まっており、疾病の予防や改善において極めて重要な免疫機能を、正常に維持することができる食品や医薬品の開発が強く望まれている。 As the aging progresses, awareness of health is increasing more and more, and there is a strong demand for the development of foods and pharmaceuticals that can maintain the immune function, which is extremely important in the prevention and amelioration of diseases, normally.
これまでに免疫調整剤として、乳酸菌ラクトコッカス・ラクティス・サブスピーシーズクレモリス Ｈ−６１株（ＮＩＴＥ ＡＰ−９２）を含有することを特徴とする免疫調整剤（特許文献１）、カテキン類を有効成分とする免疫調整剤（特許文献２）及びコエンザイムＱ１０とザクロ加工物とを含有する免疫調整剤（特許文献３）等が開示されている。 An immunomodulator (patent document 1) characterized by containing a lactic acid bacterium Lactococcus lactis subspecies cremoris H-61 strain (NITE AP-92) as an immunomodulator to date, and catechins as active ingredients. The immunomodulator (Patent Document 2) and the immunomodulator containing Coenzyme Q10 and the processed pomegranate (Patent Document 3) are disclosed.
本発明は、天然物由来の新規な免疫調整剤を提供する。 The present invention provides novel immunomodulators derived from natural products.
発明者らは、枯草菌の芽胞形成能欠損株に優れた免疫調整効果があることを見出し、本発明を完成した。 The present inventors have found that a spore-forming strain of Bacillus subtilis has an excellent immunomodulatory effect, and completed the present invention.
すなわち、本発明は、以下の［１］〜［７］の態様に関する。
［１］枯草菌の芽胞形成能欠損株を有効成分とする、免疫調整剤。
［２］脾臓細胞増殖促進用、インターフェロン−γ産生促進用又はインターロイキン−１０産生促進用である、［１］記載の免疫調整剤。
［３］枯草菌の芽胞形成能欠損株を有効成分とする、抗アレルギー剤。
［４］枯草菌の芽胞形成能欠損株を有効成分とする、免疫賦活剤。
［５］［１］又は［２］に記載の免疫調整剤を含む飲食品、化粧品、医薬品又は飼料。
［６］［３］に記載の抗アレルギー剤を含む飲食品、化粧品、医薬品又は飼料。
［７］［４］に記載の免疫賦活剤を含む飲食品、化粧品、医薬品又は飼料。That is, the present invention relates to the following aspects [1] to [7].
[1] An immunomodulator comprising a spore-forming strain of Bacillus subtilis as an active ingredient.
[2] The immunomodulator according to [1], which is for spleen cell growth promotion, interferon-γ production promotion or interleukin-10 production promotion.
[3] An antiallergic agent comprising a spore-forming strain of Bacillus subtilis as an active ingredient.
[4] An immunostimulant containing a Bacillus subtilis spore-deficient strain as an active ingredient.
[5] Food and drink, cosmetics, pharmaceuticals or feed containing the immunomodulator according to [1] or [2].
[6] Food and drink, cosmetics, pharmaceuticals, or feed containing the antiallergic agent according to [3].
[7] Food and drink, cosmetics, pharmaceuticals or feed containing the immunostimulant according to [4].
本発明によって、天然物由来の新規な免疫調整剤を提供できる。また、殺菌後の死菌において免疫調整効果が認められることから、死菌体を使用することで、製造設備の衛生管理や製品の品質管理が容易になり、免疫調整剤を効率的に製造できる。また、有効成分が化学合成品ではなく、食経験のある菌のため、継続した長期的な摂取が望ましい免疫調整剤として最適である。さらに、芽胞形成能欠損株のため、一般的な微生物と同様に１００℃以下の穏和な条件で殺菌を行うことができ、芽胞菌で問題となる殺菌不足による製造設備の汚染を防ぐことができるため、各種食品への添加や製剤化が容易である。 The present invention can provide a novel immunomodulator derived from a natural product. In addition, since an immunomodulatory effect is observed in killed bacteria after sterilization, use of killed bacteria facilitates hygiene control of manufacturing facilities and product quality control, and enables efficient production of immunomodulators. .. In addition, since the active ingredient is not a chemically synthesized product but a bacterium that has experienced eating, it is optimal as an immunomodulator that is desired to be taken continuously over a long period. Further, since it is a spore-forming ability-deficient strain, it can be sterilized under mild conditions of 100° C. or less like general microorganisms, and it is possible to prevent contamination of production facilities due to insufficient sterilization, which is a problem with spore-forming bacteria. Therefore, it is easy to add it to various foods and formulate it.
本発明は、芽胞形成能欠損株を有効成分とする免疫調整剤に関するものであって、脾臓細胞増殖促進用、インターフェロン−γ産生促進用又はインターロイキン１０産生促進用として使用でき、脾臓細胞増殖促進効果、インターフェロン−γ産生促進効果又はインターロイキン１０産生促進効果の少なくとも１つを有し、好ましくは全ての効果を有し、抗アレルギー剤又は免疫賦活剤としても有効である。 The present invention relates to an immunomodulator comprising a spore-forming ability-deficient strain as an active ingredient, which can be used for promoting spleen cell growth, promoting interferon-γ production or
本発明に記載の芽胞形成能欠損株は、免疫調整剤の有効成分となる枯草菌（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ）芽胞形成能欠損株であれば、特に限定されないが、変異前の野生株はバチルス・サブチリス・サブスピーシーズ・サブチリス（Ｂ．ｓｕｂｔｉｌｉｓ．ｓｕｂｓｐ．ｓｕｂｔｉｌｉｓ）が好ましく、バチルス・サブチリスＮＢＲＣ３００９、バチルス・サブチリスＮＢＲＣ３０１３、バチルス・ザブチリスＮＢＲＣ１３１６９等の納豆菌がより好ましく、独立行政法人製品評価技術基盤機構等から入手することができる。 The spore-forming ability-deficient strain described in the present invention is not particularly limited as long as it is a Bacillus subtilis spore-forming ability-deficient strain which is an active ingredient of an immunomodulator, but the wild-type strain before mutation is Bacillus subtilis Subspecies subtilis (B. subtilis. subsp. subtilis) is preferable, Bacillus subtilis NBRC3009, Bacillus subtilis NBRC3013, Bacillus subtilis NBRC13169, etc. are more preferable, and they are obtained from an independent administrative agency product evaluation technology foundation etc. be able to.
前記の野生株を、遺伝子組換えによる方法、突然変異による方法等により変異させることで、芽胞形成能欠損株が得られるが、自然突然変異による方法が好ましい。自然突然変異による芽胞形成能欠損株の取得方法は、特に限定されず、高温培養法や、野生株と欠損株のコロニーのメラニン色素の着色により識別するランダム法、異化代謝産物抑制（Ｃａｔａｂｏｌｉｔｅ ｒｅｐｒｅｓｓｉｏｎ）様現象を利用した方法（Ｊ．Ｆ．Ｍｉｃｈｅｌ，Ｂ．Ｃａｍｉ，Ｐ．Ｓｃｈａｅｆｆｅｒ：Ａｎｎ．Ｉｎｓｔ．Ｐａｓｔｅｕｒ，１１４，１１；２１（１９６８））が例示できるが、異化代謝産物抑制様現象を利用した方法が好ましい。異化代謝産物抑制様現象を利用する方法により得られる芽胞形成能欠損株は、芽胞形成能と供にリゾチーム活性及び形質転換能が欠損しているため、溶菌による問題がなく継代することができ、芽胞形成能欠損という形質を維持することができる。芽胞形成能欠損株を使用すれば、本発明の免疫調整剤の有効成分とすることができる他、１００℃以下の穏和な殺菌条件で死菌体を調製することができるため、芽胞形成株で問題となる殺菌不足による製造設備の汚染を防ぐことができ、各種食品への添加や製剤化が容易となる。また、生菌でも死菌でも免疫調整効果を有するが、死菌体を使用するのが好ましく、死菌体を使用することで、製造設備の衛生管理や製品の品質管理が容易になり、免疫調整剤を効率的に製造できる。 By mutating the above wild strain by a method such as gene recombination or mutation, a spore-forming ability-deficient strain can be obtained, but a method by spontaneous mutation is preferable. The method for obtaining a strain deficient in spore-forming ability by natural mutation is not particularly limited, and it is a high temperature culture method, a random method for discriminating the colonies of the wild type strain and the defective strain by coloring the melanin pigment, or catabolite suppression (catabolite repression). A method utilizing such a phenomenon (J. Michel, B. Cami, P. Schaeffer: Ann. Inst. Pasteur, 114, 11; 21 (1968)) can be exemplified, but a catabolic metabolite inhibition-like phenomenon was used. The method is preferred. The spore-forming ability-deficient strain obtained by the method utilizing the catabolite repression-like phenomenon is deficient in lysozyme activity and transforming ability in addition to the spore-forming ability, and therefore can be passaged without problems due to lysis. It is possible to maintain the trait of defective spore formation. If a spore-forming strain-deficient strain is used, it can be used as an active ingredient of the immunomodulator of the present invention, and killed cells can be prepared under mild sterilization conditions of 100° C. or lower. Contamination of manufacturing equipment due to insufficient sterilization can be prevented, which facilitates addition to various foods and formulation. In addition, both live and dead bacteria have an immunoregulatory effect, but it is preferable to use dead cells, and by using dead cells, hygiene control of manufacturing facilities and product quality control become easier, The regulator can be efficiently produced.
芽胞形成能欠損株の培養には、通常の細菌培養用培地が使用でき、炭素源、窒素源、無機物、その他枯草菌が必要とする微量栄養素等を含有するものであれば、合成培地、天然培地の何れでも使用可能である。炭素源としては、グルコース、シュクロース、デキストリン、澱粉、グリセリン、糖蜜等が使用できる。窒素源としては、塩化アンモニウム、硝酸アンモニウム、硫酸アンモニウム、リン酸アンモニウム等の無機塩類、ＤＬ−アラニン、Ｌ−グルタミン酸等のアミノ酸類、ペプトン、肉エキス、酵母エキス、麦芽エキス、コーンスティープリカー等の窒素含有天然物が使用できる。無機物としては、リン酸一ナトリウム、リン酸二ナトリウム、リン酸一カリウム、リン酸二カリウム、硫酸マグネシウム、塩化第二鉄等が使用できる。 For culturing the spore-forming ability deficient strain, an ordinary bacterial culture medium can be used, and if it contains a carbon source, a nitrogen source, an inorganic substance, and other micronutrients required by Bacillus subtilis, a synthetic medium, a natural medium Any of the culture media can be used. As the carbon source, glucose, sucrose, dextrin, starch, glycerin, molasses, etc. can be used. As a nitrogen source, inorganic salts such as ammonium chloride, ammonium nitrate, ammonium sulfate and ammonium phosphate, amino acids such as DL-alanine and L-glutamic acid, nitrogen containing such as peptone, meat extract, yeast extract, malt extract and corn steep liquor Natural products can be used. As the inorganic substance, monosodium phosphate, disodium phosphate, monopotassium phosphate, dipotassium phosphate, magnesium sulfate, ferric chloride and the like can be used.
培養条件は、適宜設定できるが、通気、振盪、攪拌等により好気的に液体培養するのが好ましく、培養温度は例えば２０〜５０℃が例示でき、３０〜４５℃が好ましく、培養時間は例えば２〜７２時間が例示でき、４〜４８時間が好ましく、６〜３６時間がより好ましく、培地のｐＨは例えば５．０〜９．０が例示でき、５．５〜８．５が好ましい。 The culture conditions can be appropriately set, but it is preferable to perform aerobic liquid culture by aeration, shaking, stirring, etc., and the culture temperature can be exemplified at 20 to 50° C., preferably 30 to 45° C., and the culture time is, for example, It can be exemplified for 2 to 72 hours, preferably 4 to 48 hours, more preferably 6 to 36 hours, and the pH of the medium can be, for example, 5.0 to 9.0, and preferably 5.5 to 8.5.
培養後に殺菌してもよく、殺菌条件は一般的な方法であれば特に限定されないが、例えば加熱温度は、７０〜１５０℃であり、加熱時間は、温度に応じて決定すればよいが、通常１〜６０分である。また本発明に記載の芽胞形成能欠損株は、芽胞を形成しないため、１００℃以下の穏和な条件で殺菌を行うことができ、例えば７０〜１００℃、５〜２０分間の加熱が例示できる。本発明に記載の芽胞形成能欠損株は、芽胞菌で問題となる殺菌不足による製造設備の汚染を防ぐことができるため、各種食品への添加や製剤化が容易である。菌体の回収は、遠心分離機等で培地を除去した後、緩衝液、生理食塩水、滅菌水等で菌体を洗浄し、遠心分離機等により固液分離して集菌できる。さらに、エアードライ、スプレードライ、真空及び／又は凍結乾燥等を行って粉末化してもよい。 It may be sterilized after culturing, and the sterilization condition is not particularly limited as long as it is a general method, for example, the heating temperature is 70 to 150° C., and the heating time may be determined according to the temperature, but is usually 1 to 60 minutes. Further, the spore-forming ability-deficient strain described in the present invention does not form spores, and thus can be sterilized under mild conditions of 100°C or lower, and for example, heating at 70 to 100°C for 5 to 20 minutes can be exemplified. The spore-forming ability-deficient strain described in the present invention can prevent contamination of production facilities due to insufficient sterilization, which is a problem with spore-forming bacteria, and thus can be easily added to various foods or formulated. The cells can be collected by removing the medium with a centrifuge or the like, washing the cells with a buffer solution, physiological saline, sterilized water or the like, and separating the solid and liquid with a centrifuge or the like to collect the cells. Further, it may be pulverized by air drying, spray drying, vacuum and/or freeze drying.
本発明の免疫調整剤、抗アレルギー剤又は免疫賦活剤はその有効成分が天然物由来であり、かつ、製造が容易なため、広く利用でき、各種製品に添加が可能で、液状で添加してもよく、冷蔵、冷凍又は乾燥状態で添加してもよく、免疫調整効果、抗アレルギー効果又は免疫賦活効果を有する飲食品、化粧品、医薬品、飼料等を調製することができる。各種製品中の枯草菌含有量は、摂取により効果が認められる量であれば特に限定されないが、０．１〜２０重量％が好ましく、０．２〜１０重量％がより好ましく、０．５〜５重量％がさらに好ましい。 Since the active ingredient of the immunomodulator, antiallergic agent or immunostimulant of the present invention is derived from a natural product and is easy to manufacture, it can be widely used and can be added to various products. Alternatively, it may be added in a refrigerated, frozen or dried state, and foods and drinks, cosmetics, pharmaceuticals, feeds and the like having an immunomodulating effect, an antiallergic effect or an immunostimulating effect can be prepared. The Bacillus subtilis content in various products is not particularly limited as long as the effect is recognized by ingestion, but is preferably 0.1 to 20% by weight, more preferably 0.2 to 10% by weight, and 0.5 to 5% by weight is more preferred.
以下、実施例を示して本発明を具体的に説明するが、本発明は以下の例によって限定されるものではない。尚、本発明において、％は別記がない限り全て重量％である。 Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples. In the present invention, all percentages are by weight unless otherwise specified.
（芽胞形成能欠損株の死菌体粉末の調製）
異化代謝産物抑制様現象を利用した自然突然変異により、納豆菌の一種であるバチルス・サブチリスＮＢＲＣ１３１６９から、芽胞形成能を欠損した、芽胞形成能欠損株：バ
A spore formation-deficient strain, Bacillus subtilis NBRC13169, which is a kind of Bacillus subtilis natto, which has a spore formation-deficient strain:
前記枯草菌を、液体培地（酵母エキス：２％、グルコース：５％、水道水：９３％）に接種して３７℃で２４時間通気攪拌培養した後、９０℃で１０分間加熱殺菌処理した（一般生菌数：１０個／ｇ未満）。次いで、遠心分離機を用いて培地を除去し、回収した菌体を水道水で洗浄した後、さらに遠心分離機で固液分離することで、菌体を回収した。回収した菌体をスプレードライヤーで乾燥し、枯草菌の芽胞形成能欠損株の死菌体粉末（実施品１、一般生菌数：１０２個／ｇ未満）を調製した。The Bacillus subtilis was inoculated into a liquid medium (yeast extract: 2%, glucose: 5%, tap water: 93%), cultured at 37°C for 24 hours with aeration and stirring, and then heat-sterilized at 90°C for 10 minutes ( General viable cell count: less than 10 cells/g). Next, the culture medium was removed using a centrifuge, the collected bacterial cells were washed with tap water, and then subjected to solid-liquid separation with a centrifugal separator to recover the bacterial cells. The collected bacterial cells were dried with a spray drier to prepare dead bacterial cell powder of Bacillus subtilis spore-deficient strain (Example 1, general viable cell count: less than 10 2 cells/g).
［比較例１］
（芽胞形成株の死菌体粉末の調製）
実施例１記載のバチルス・サブチリスＮＢＲＣ１３１６９を未変異のまま使用し、実施例１と同様に培養した後、１２１℃で１５分間加熱殺菌処理した（一般生菌数：１０個／ｇ未満）。次いで、実施例１と同様に処理し、枯草菌の芽胞形成株の死菌体粉末（比較品１、一般生菌数：１０２個／ｇ未満）を調製した。
尚、未変異株は芽胞形成株のため、実施例１と同じ殺菌条件９０℃、１０分間処理では、一般生菌数３．０×１０６個／ｇと殺菌できなかったため、１２１℃、１５分間の処理とした。[Comparative Example 1]
(Preparation of dead bacterial cell powder of spore forming strain)
The Bacillus subtilis NBRC13169 described in Example 1 was used as it was without mutation, and after culturing in the same manner as in Example 1, heat sterilization treatment was performed at 121° C. for 15 minutes (general viable count: less than 10 cells/g). Then, the same treatment as in Example 1 was carried out to prepare dead cell powder of a spore-forming strain of Bacillus subtilis (Comparative product 1, general viable cell count: less than 10 2 cells/g).
Since the unmutated strain was a spore-forming strain, it could not be sterilized with a general viable cell count of 3.0×10 6 cells/g under the same sterilization conditions of 90° C. and 10 minutes as in Example 1, so 121° C., 15 It was treated for a minute.
［評価試験１］
（脾臓細胞増殖促進作用）
ＢＡＬＢ／ｃマウスの脾臓から採取した脾臓細胞を細胞培養プレートに播き、実施品１もしくは比較品１の菌体粉末を５０μｇ／ｍｌとなるようにそれぞれ添加、又は菌体粉末添加無しで、３７℃で３０時間培養した後、ブロモデオキシウリジン（ＢｒｄＵ）を添加した。さらに１８時間培養した後、標識済み抗ＢｒｄＵ抗体を用いて発色させ、４５０ｎｍの吸光度（ＯＤ４５０）を測定することにより、脾臓細胞の増殖能を評価した。各群３ウェルずつ実施し、各群のＯＤ４５０（平均値）及び標準偏差を算出し、表１及び図１に示した。また、比較品１の値を１とした場合の実施品１の相対値について算出し、表１に示した。[Evaluation test 1]
(Spleen cell growth promoting action)
Spleen cells collected from the spleens of BALB/c mice were seeded on a cell culture plate, and the bacterial cell powder of Example 1 or Comparative Product 1 was added at 50 μg/ml, respectively, or the bacterial cell powder was not added at 37° C. After culturing at 30° C. for 30 hours, bromodeoxyuridine (BrdU) was added. After further culturing for 18 hours, a labeled anti-BrdU antibody was used for color development, and the absorbance at 450 nm (OD450) was measured to evaluate the proliferation ability of spleen cells. 3 wells were carried out for each group, and the OD450 (average value) and standard deviation of each group were calculated and shown in Table 1 and FIG. Further, the relative value of the implementation product 1 when the value of the comparison product 1 was set to 1 was calculated and shown in Table 1.
表１及び図１より、実施品１を添加した細胞では、添加無し及び比較品１より高い吸光度を示すことが分かった。つまり、脾臓細胞の増殖が、枯草菌の芽胞形成株の添加よりも芽胞形成能欠損株添加により促進されることが分かり、枯草菌の芽胞形成能欠損株が優れた細胞増殖促進作用を有し、芽胞形成株の添加に比べ約１．２倍も促進されることが分かった。 From Table 1 and FIG. 1, it was found that the cells to which the product 1 was added exhibited higher absorbance than the cells without the addition and the comparative product 1. That is, it was found that the growth of spleen cells was promoted by the addition of the sporulation-deficient strain of Bacillus subtilis to the addition of the sporulation-deficient strain of Bacillus subtilis, and the strain of Bacillus subtilis lacking the sporulation ability had an excellent cell growth promoting action. It was found that the spore-forming strain was promoted about 1.2 times as much as the addition of the spore-forming strain.
よって、枯草菌の芽胞形成能欠損株は、脾臓細胞の増殖促進作用がみられたことから、免疫を強化する免疫賦活効果が期待できる。 Therefore, the spore formation-deficient strain of Bacillus subtilis has a spleen cell growth-promoting action, and thus an immunostimulatory effect of enhancing immunity can be expected.
［評価試験２］
（サイトカイン産生促進作用）
ＢＡＬＢ／ｃマウスの脾臓から採取した脾臓細胞を、予め、Ｔ細胞活性化抗体である抗ＣＤ３抗体０〜２μｇ／ｍＬで処理した細胞培養プレートに播き、実施品１もしくは比較品１の菌体粉末を５０μｇ／ｍｌとなるようにそれぞれ添加、又は菌体粉末添加無しで、３７℃で４８時間培養した後、ＥＬＩＳＡ法によりインターフェロン−γ（ＩＦＮ−γ）濃度又はインターロイキン−１０（ＩＬ−１０）濃度を測定した。各群３ウェルずつ実施し、抗ＣＤ３抗体処理無し（Ｔ細胞の活性化未実施）の細胞培養プレート各群の平均値及び標準偏差を算出し、表２に示した。また、比較品１の値を１とした場合の実施品１の各相対値について算出し、表２に示した。さらに、ＩＦＮ−γ濃度又はＩＬ−１０濃度について、各抗ＣＤ３抗体濃度における細胞培養プレート各群の平均値及び標準偏差を算出し図２に示した。[Evaluation test 2]
(Cytokine production promoting action)
Spleen cells collected from the spleen of a BALB/c mouse were seeded on a cell culture plate previously treated with an anti-CD3 antibody that is a T
表２より、抗ＣＤ３抗体で処理していない細胞において、菌体粉末を添加しなかった細胞がほとんどＩＦＮ−γ及びＩＬ−１０の産生が見られなかったのに対し、比較品１及び実施品１の菌体粉末を添加した細胞では、ＩＦＮ−γ及びＩＬ−１０が何れも産生されていた。さらに実施品１を添加した細胞では、比較品１を添加した細胞に比べ、ＩＦＮ−γ産生量が２．８倍、ＩＬ−１０産生量が１．１倍と、ＩＦＮ−γ及びＩＬ−１０の産生がより促進されていた。つまり、Ｔ細胞の活性化を行うことで通常産生されるＩＦＮ−γ及びＩＬ−１０が、Ｔ細胞の活性化を行わなくとも、枯草菌の死菌体粉末の添加で産生され、さらに、芽胞形成能欠損株の死菌体粉末の添加により、より促進されることが分かった。
また、図２より、ＩＦＮ−γ及びＩＬ−１０の産生量は、抗ＣＤ３抗体の濃度に比例して増加しており、特に比較品１を添加した細胞より、枯草菌の芽胞形成能欠損株である実施品１を添加した細胞でより顕著な増加がみられた。From Table 2, in the cells not treated with the anti-CD3 antibody, almost no IFN-γ and IL-10 production was observed in the cells to which the bacterial cell powder was not added, whereas the comparative product 1 and the working product. Both IFN-γ and IL-10 were produced in the cells to which the cell powder of No. 1 was added. Furthermore, in the cells to which the product 1 was added, the amount of IFN-γ produced was 2.8 times and the amount of IL-10 produced was 1.1 times that of the cells to which the comparative product 1 was added, and IFN-γ and IL-10. Was more accelerated. That is, IFN-γ and IL-10 that are normally produced by activating T cells are produced by the addition of dead Bacillus subtilis cell powder even if T cells are not activated, and It was found that the addition of the dead cell powder of the forming-deficient strain further promoted.
Further, from FIG. 2, the production amounts of IFN-γ and IL-10 increased in proportion to the concentration of the anti-CD3 antibody, and particularly from the cells to which the comparative product 1 was added, the spore-forming strain of Bacillus subtilis was defective. A more remarkable increase was observed in the cells to which the product 1 of Example 1 was added.
ＩＦＮ−γの産生が促進されることで、マクロファージやナチュラルキラー細胞が活性化され、抗腫瘍作用や感染防御等の細胞性免疫賦活効果を発揮すると思われる。さらに、タイプ１ヘルパーＴ細胞（Ｔｈ１）であるＩＦＮ−γの産生が促進されることで、タイプ２ヘルパーＴ細胞（Ｔｈ２）が抑制されるため、抗アレルギー効果を発揮すると思われる。また、免疫抑制サイトカインであるＩＬ−１０の産生が促進されることで、Ｔｈ２が抑制されるため、過剰な炎症反応を抑え、抗アレルギー効果を発揮すると思われる。 It is considered that by promoting the production of IFN-γ, macrophages and natural killer cells are activated, and a cell-mediated immunostimulatory effect such as an antitumor effect and infection defense is exhibited. Furthermore, since production of IFN-γ, which is a type 1 helper T cell (Th1), is promoted and
評価試験１及び２の結果から、枯草菌芽胞形成能欠損株の死菌体粉末の添加により、強力な脾臓細胞増殖促進作用、ＩＦＮ−γ産生促進作用及びＩＬ−１０産生促進作用がみられたことから、枯草菌の芽胞形成能欠損株は、免疫賦活効果や抗アレルギー効果が期待でき、枯草菌の芽胞形成能欠損株を有効成分とした、アレルギー疾患、自己免疫疾患等免疫系疾患の予防又は改善剤、免疫賦活剤等に使用可能な免疫調整剤として有用と思われる。 From the results of Evaluation Tests 1 and 2, a strong spleen cell growth promoting action, an IFN-γ production promoting action and an IL-10 production promoting action were observed by the addition of dead cell powder of the Bacillus subtilis spore-forming strain deficient strain. Therefore, the Bacillus subtilis spore-forming ability-deficient strain can be expected to have an immunostimulatory effect and an anti-allergic effect, and the Bacillus subtilis spore-forming ability-deficient strain is used as an active ingredient to prevent allergic diseases, autoimmune diseases, and other immune system diseases. Alternatively, it is considered to be useful as an immunomodulator that can be used as an improving agent, an immunostimulant and the like.
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| APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, vol. 101, no. 14, JPN6022041326, pages 5819 - 5829, ISSN: 0004886902 * |
| MICROBIOLOGY AND IMMUNOLOGY, vol. 56, no. 12, JPN6022041325, 2012, pages 817 - 824, ISSN: 0004886901 * |
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