| Identification | Back Directory | [Name]
HUMAN LEUKOCYTE IFN | [CAS]
284690-33-1 | [Synonyms]
IFL
IFN
IFNA13
α-IFN-Le
INTERFERON
HUMAN LEUKOCYTE IFN
Interferon-γ human
Interferon-γ porcine
Interferon β from rat
HUMAN LEUKOCYTE INTERFERON
Interferon β from mouse
Interferon from human leukocytes
ANTI-IFNA1 antibody produced in mouse | [MDL Number]
MFCD00131393 |
| Hazard Information | Back Directory | [Uses]
Interferon-γ from mouse has been used:
- for in vitro stimulation of the BMDC (bone marrow derived dendritic cell), BMM (bone marrow-derived macrophages) and CD11c+ (CD11 antigen-like family member C) lung macrophages
- for stimulation of murine macrophages to induce the production of nitrite and nitrate
- to check CCAAT/enhancer binding protein β (C/EBPβ)-mediated changes in the expression of prostaglandin synthesis enzymes in neuroinflammation
| [Pharmaceutical Applications]
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. | [Biological Activity]
In presence of virus infectionIFN β (interferon β) is upregulated and plays a crucial role in innate antiviral response. It is also important for anti-inflammatory effects.''Interferon β (IFN-β) suppresses a variety of proinflammatory cytokines in lymphocytes including the interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). It also favors the synthesis of antagonists associated with interleukin IL-10 and IL-1 receptor. IFN-β downregulates interferon γ production but enhances transforming growth factor β1 expression. It has therapeutic potential in treating rheumatoid arthritis and relapsing-remitting multiple sclerosis (MS).''Interferon β has a role in the | [Mechanism of action]
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. | [Pharmacokinetics]
Oral absorption: Poor
Cmax 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. | [Clinical Use]
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. | [Side effects]
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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