Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Separation or purification
Patent
1996-05-20
1999-05-11
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Separation or purification
530351, A23J1/00
Patent
active
059028777
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to an adsorbent of interleukins, a process for removing the same, and an adsorber of the same. More particularly, the present invention relates to the adsorbent which adsorbs at least one interleukin selected from the group consisting of interleukin-8 (hereinafter referred to as IL-8), interleukin-1.beta. (hereinafter referred to as IL-1.beta.), interleukin-6 (hereinafter referred to as IL-6) and interleukin-2 (hereinafter referred to as IL-2) and to the process for removing and the adsorber by means of the above-mentioned adsorbent.
BACKGROUND ARTS
A cytokine is a greatly important proteinous substance as a biophylactic factor which closely relates to various kinds of antigen-specific, non-specific immune inflammatory responses. The existance thereof is necessary and indispensable for maintaining biological homeostasis and the cytokine is produced excessively in a disease with inflammation, relating to the formation and the prolongation of pathology of the disease.
"IL-8" is one kind of cytokine purified as a monocyte-derived neutrophil chemotactic factor (MDNCF) by Matsushima et al. and gene thereof has also been cloned in 1987. IL-8 is a neutrophile-activation migration regulatory factor produced by various kinds of cells.
It is known that IL-8 acts on a neutrophil to enhance functions for inhibiting growth of Candida albicans and Mycobacterium which the neutrophil has, and it is anticipated that IL-8 has an effect as an immunoactivation agent (Nipponigakukan, Cytokine--From Foundation to The Latest Information--, 1991, pages 65-72). Therefore, there has been desired a method for efficiently purifying IL-8 in a large amount from a body fluid or a culture medium.
On the other hand, the continuous administration of IL-8 in a large amount is remarkably harm to tissues, and causes the destruction of tissues of adult respiratory distress syndrome in an alveolus and the destruction of tissues with the infiltration of lymphocytes in a large amount in an arthrosis. Experimentally, it is shown that IL-8 relates essentially to the infiltration of neutrophils in dermatitis derived from lipopolysaccharide (LPS) and during reperfusion after ischemia. This has been proved by the fact that the destruction of tissues accompanied by the above-mentioned infiltration of lymphocytes or neutrophils can be inhibited almost completely by administrating a neutralizing antibody against IL-8. Further, an abnormally higher concentration of IL-8 has been detected in an inflammatory site or in peripheral blood of patients with diseases such as rheumatoid arthritis (RA), gouty arthritis, psoriasis, contact dermatitis, septicemia, idiopathic fibroid lung, adult respiratory distress syndrome, inflammatory bowel disease, immune angiitis, glomerular nephritis, urinary tract infection, cardiac infarction, asthma, respiratory tract infection, perinatal infectious disease and rejection in organ transplantation, than that of a normal human (refer to Menekiyakuri, 12, No. 1, pages 15-21 (1994)). And, it is considered that IL-8 relates to these diseases. At present, however, an efficient method to inhibit the function of IL-8 in these diseases has not been established.
Then, "IL-1.beta." is an inflammatory cytokine which is produced mainly by a monocyte and/or a macrophage with stimulation by a foreign matter such as bacteria, and in 1984, the gene of human has been cloned by Auron et al.
As seen from the fact that IL- 1.beta. has been discovered as an endogenious pyrogen (EP), a leukocytic endogenious mediator (LEM), a lymphocyte activation factor (LAF), a B cell-activating factor (BAF) and the like until the standardized name of interleukin 1 (IL-1) was determined as the same substance at The 2nd International Lymphokine Workshop in 1979, the bioactivity thereof is shown in various functions.
Though IL-1.beta., which is a main mediator of an inflammation, plays an important role in various kinds of reactions including homeostasis of a living body in the ordinary state, it has been clear that
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Yabuki et al., "Container Containing Anionic Adsorbent", CAPLUS # 1991:542398, Jan. 24, 1991.
Nakatani et al., "Adsorbent & Methods for Removing Chemokines" CAPLUS # 1997:671643, Sep. 24, 1997.
Sakurai et al., "Purification of IL-8" CAPLUS # 1993:579163, Jul. 9, 1993.
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Asahi Takashi
Hirai Fumiyasu
Nomura Michio
Odawara Osamu
Okubo Yuji
Delaney Patrick R.
Kanegafuchi Kagaku Kogyo & Kabushiki Kaisha
Tsang Cecilia J.
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