INDEX（目次）に戻るD.J.Ormrod and T.E.Miller
ABSTRACT
"Immune" milk has been utilized as a source of biologically
active compounds for many years. In the present study, a low molecular
weight fraction, isolated from the milk of dairy cows hyperimmunized
with a multivalent bacterial vaccine (HIMF), has been evaluated
for anti-inflammatory activity. Analysis was carried out using
the rat hind-paw oedema assay. HIMF was shown to have a marked
anti-inflammatory effect in this model and carrageenin-induced
oedema was suppressed by up to 80% in individual experiments.
The agent was active following oral, subcutaneous, intramuscular,
intraperitoneal or intravenous administration. Intravenous injection
was particularly effective, and amount as small as 1 mg significantly
reduced the inflammatory response to carrageenin. The experiments
have established that milk from hyperimmunized cows contains a
highly active anti-inflammatory compound and form a basis for
further studies, which will attempt to isolate and further characterize
the active moiety.
Agents and Actions. vol.32,3/4 (1991)
●日本語訳
“免疫”ミルクは長年、生物学的活性をもつ複合物として利用されてきた。最近の研究 において、多価性のワクチンにより免役された乳牛のミルクから分離された低分子分画（ HIMF）の抗炎症活性が評価されている。分析はラットの後ろ足浮腫を用いた分析法を用い て行われた。HIMFはこのモデルにおいて注目すべき抗炎症効果を示し、個別の実験におい てカラギーナン誘導による浮腫を最高で80%抑制した。この物質は経口、皮下、筋肉内、 腹腔内、静脈内への投与において活性を示した。静脈注射は特に効果が高く、カラギーナ ンへの炎症応答を1mg程度で顕著に抑制した。この実験により、免役したウシより得られ たミルクには、高い抗炎症活性を持った物質が含まれており、次の研究として、活性部分 を分離し、より特徴づける研究への基礎を成す。
Douglas J. Ormrod and Thomas E. Miller
ABSTRACT
An earlier study demonstrated that hyperimmunization of dairy
cows with a polyvalent bacterial vaccine stimulated the secretion
of a small molecular weight anti-inflammatory moiety in the milk.
This hyperimmune milk factor (HIMF) has been further investigated
in the present experiments. HIMF was found to suppress the cellular
phase of the response to carrageenin and also the neutrophil-dependent
reverse passive Arthus reaction. These results, together with
the observation that the administration of HIMF led to an increase
in the number of circulating neutrophils, suggested that the agent
might inhibit inflammation by interfering with the ability of
neutrophils to emigrate from the vasculature. In vivo studies
carried out to evaluate this possibility demonstrated that HIMF
suppressed neutrophil emigration by up to 75%. In vivo experiments
established that the ability of neutrophils to respond to chemotactic
stimuli or adhere to endothelial cells was not affected by HIMF.
It is possible, therefore, that the agent modulates inflammation
by down-regulating the synthesis of inducible pro-inflammatory
cytokines or adhesion molecules. Attempts are presently being
made to isolate the active moiety to allow the activity of the
agent at the molecular level to be studied in more detail.
ABSTRACT 2
The invention relates to a method for inducing the production
of a milk anti-hypertensive factor in an animal, to a method for
the isolation of said factor from the milk of said animal in a
substantially pure form, and to the use of said factor to treat
hypertension in humans and other animals.
SUMMARY OF THE INVENTION
The present inventors have previously disclosed hyperimmune bovid
milk with anti-inflammatory effects and with beneficial effects
against vascular, pulmonary, and gastrointestinal disorders. The
beneficial vascular effects of the hyperimmune bovid milk prompted
the present inventors to investigate possible effects of the milk
on elevated arterial pressure in humans and other animals. With
this in mind, the inventors then made the unexpected discover
that milk obtained from cows hyperimmunized against certain bacterial
antigens (i.e., the hyperimmune milk of the invention), when administered
orally to hypertensive subjects, dramatically decreased the blood
pressure to normotensive values, and did so without any detectable
undesirable side effects. It was also discovered that milk of
non- hyperimmunized cows also contains anti-hypertension activity,
but that this activity is greatly enhanced by the hyperimmunization
of the donor cow. Therefore, the invention relates to a method
of production of hyperimmune bovid milk, a composition of said
milk suitable for administration to a subject, and to the use
of said composition to reduce elevated arterial pressure in such
subjects.
Agents and Actions. vol.35 (1992)
●日本語訳
これまでの研究で、乳牛を多価の細菌によるワクチンで免疫することが、低分子量の抗 炎症成分の分泌を刺激することが示されている。この超免疫ミルク因子（HIMF）に関し、 本研究によりさらに調査した。HIMFはカラギーナンに対する反応の細胞相及び好中球依存 の逆受動アルチュス反応を抑制することが分かっている。HIMFの摂取により、循環してい る好中球数を増加が観察された事と合わせ、これらの結果により、この成分が、静脈から 遊走する好中球の能力を阻害することにより炎症を抑制する可能性を示唆している。 この可能性を確定するために行われたIn vivoの研究によりHIMFが好中球の遊走を最高75% 抑制することが示された。In vitroの研究では、好中球の化学的刺激剤に対する応答もし くは内皮細胞の吸着能力はHIMFに影響されなかった。そのため、この成分は、炎症を誘導 するサイトカインや接着分子の親和性を抑制することにより、炎症を変化させる可能性が ある。この成分の活性を分子レベルでより詳細に解明するために、この活性成分を分離す る試みが、現在成されている。