インターフェロン

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インターフェロン 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.

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