HUMAN LEUKOCYTE IFN 化学特性,用途語,生産方法
解説
略称IFN．抗ウイルス作用を有するタンパク質で，IFNα，IFNβ，IFNγのサブタイプがある．1個の細胞にウイルスを同時に2種類感染させようとすると，その2種類のウイルスが共生的に細胞内で増殖する場合と，一方のウイルス増殖がほかのウイルスによって阻止される場合とがある．この感染阻止作用をもつ物質はウイルス粒子そのものではないことが明らかになり，これをインターフェロンとよんだ．感染阻止は特異的な免疫とは関係なく，ウイルス，またはその断片や増殖力のないウイルスとの接触によっても，またトキソイド，核酸，リケッチャ，細菌，抗生物質ばかりでなく，物理的刺激でも誘発される．Ⅰ型に分類されるIFNα(白血球由来)とIFNβ(繊維芽細胞由来)は比較的似ており，Ⅱ型に分類されるIFNγはこれらと少し異なる．C型肝炎の治療に効果があることから一時注目された．[CAS 9008-11-1]
森北出版「化学辞典（第2版）
応用例（製薬）
A human protein produced by recombinant DNA technology
in Escherichia coli, formulated for administration by
intramuscular, subcutaneous or intralesional injection. A
pegylated form, peginterferon, developed by attaching a 40
kDa branched-chain polyethylene glycol moiety to interferon-
α-2a, has a prolonged half-life and is better tolerated. Potency
is expressed as international units (IU), defined as the amount
needed to prevent lysis of 50% of cells by vesicular stomatitis
virus in tissue culture assay.
作用機序
Although interferons are mediators of immune response, different mechanisms for the antiviral action of
interferon have been proposed. Interferon-α possesses broad-spectrum antiviral activity and acts on
virus-infected cells by binding to specific cell surface receptors. It inhibits the transcription and
translation of mRNA into viral nucleic acid and protein. Studies in cell-free systems have shown that the
addition of adenosine triphosphate and double-stranded RNA to extracts of interferon-treated cells
activates cellular RNA proteins and a cellular endonuclease. This activation causes the formation of
translation inhibitory protein, which terminates production of viral enzyme, nucleic acid, and structural
proteins. Interferon also may act by blocking synthesis of a cleaving enzyme required for viral
release.
薬物動態学
Oral absorption: Poor
C
max 3 × 106 IU intramuscularly: 20 IU/mL after 2–4 h
9 × 106 IU intramuscularly: 50–100 IU/mL after 2–4h
Plasma half-life: 3–8 h
Peginterferon: 36 h
Plasma protein binding: Not known
Cerebrospinal fluid (CSF) penetration is poor. It is not
cleared by hemodialysis. Little or none is excreted in the
urine, and its fate after release from the cell receptor is
largely unknown. The extent of excretion in breast milk is
unknown.
臨床応用
Chronic hepatitis B
Chronic hepatitis C (in combination with ribavirin)
Condyloma acuminata (intralesional)
It may also be of benefit in hairy cell and chronic myelogenous
leukemias and Kaposi’s sarcoma.
副作用
Toxicity has become increasingly apparent with the advent
of purer preparations. ‘Flu’-like symptoms (fever, arthralgia,
myalgia, headache, malaise, chills) occur, which can usually
be ameliorated by acetaminophen (paracetamol) administration.
Lymphocytopenia is common, generally arising 2–4 h
after administration of several million units. Liver function
test values are frequently elevated at doses above 107 IU/day.
These effects are rapidly reversible and tolerance may develop
after several doses. Other toxic effects include gastrointestinal
disturbances (anorexia, nausea, diarrhea, vomiting), weight
loss, local pain, severe fatigue, alopecia, paresthesias, confusion,
dizziness, drowsiness, nervousness and bone marrow
suppression. Neutropenia and thrombocytopenia are dose
dependent (threshold around 3 × 106 IU/day) and reversible.
Hypotension may develop during, or up to 2 days after,
treatment, and arrhythmias and cardiac failure have been
observed.
Administration of excessive doses to pregnant rhesus monkeys
in the early to mid-trimester caused abortions. Its effect
on human pregnancy is unknown. Neutralizing antibodies
have been reported in about 25% of treated patients but no
clinical sequelae to their presence have been documented.
Intralesional administration in the treatment of condylomata
acuminata is generally well tolerated.
Peginterferon is also associated with fatigue, headache,
myalgia and fever; most other side effects occur less
frequently.
HUMAN LEUKOCYTE IFN 上流と下流の製品情報
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