Emergence and decay of the human Mx homolog in cancer patients during and after interferon-alpha therapy.
The human Mx, an interferon (IFN)-alpha- and IFN-beta-induced 76-kd protein, is a homolog (Mx-homolog) to the murine Mx protein, which is necessary and sufficient to provide adequate resistance against influenza virus in murine cells and in mice. Leukocytes from 36 patients with tumors (chronic myelogenic leukemia, hairy cell leukemia, and malignant melanoma) were monitored for their Mx-homolog content before, during, and after rIFN-alpha-2b therapy. Before therapy, only one patient was slightly positive for Mx-homolog. All 36 patients showed a significant increase of Mx-homolog in their mononuclear cells within the first day of IFN therapy. During therapy, the Mx-homolog levels remained elevated. After cessation of treatment, the Mx-homolog content in the mononuclear cells decreased slowly; within 2 weeks, it was about 20-30% of its value during therapy. However, even after 3 weeks, the Mx-homolog was still detectable. The maximally induced Mx-homolog concentration showed a significant correlation to the IFN dose given in vivo. These data indicate that the Mx-homolog is an excellent marker for monitoring the activity of IFN during IFN therapy. In addition, the in vivo endogenous activation of the IFN system might be detectable by the determination of the Mx-homolog despite the lack of circulating IFN.
Jakschies
D
D
Department of Immunology and Transfusion Medicine, Medical School Hannover, F.R.G.
Hochkeppel
H
H
Horisberger
M
M
Deicher
H
H
von Wussow
P
P
D000650:Amnion / Q000166:cytology; D000911:Antibodies, Monoclonal; D002460:Cell Line; D019204:GTP-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007370:Interferon Type I / Q000494:pharmacology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D007943:Leukemia, Hairy Cell / Q000097:blood / Q000188:drug therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000032:analysis; D008545:Melanoma / Q000097:blood / Q000188:drug therapy*; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins