In vitro and in vivo effect of interleukin-2 on the 2',5'-oligoadenylate synthetase activity of peripheral mononuclear blood cells.
The in vitro and in vivo influence of interleukin-2 (IL-2) on 2',5'-oligoadenylate (2-5A) synthetase activity and natural killer (NK) activity of peripheral mononuclear blood cells (PBMCs) was investigated. Incubation of PBMCs in vitro with IL-2 resulted in a considerable secretion of interferon-gamma (IFN-gamma) and in a significant elevation of 2-5A synthetase activity, as well as NK activity. Neutralizing monoclonal anti-IFN-gamma antibodies inhibited the elevation of 2-5A synthetase activity, but not the IL-2-induced augmentation of NK activity. Additionally, 2-5A synthetase and NK activity of PBMCs was measured in a child with neuroblastoma that was treated with recombinant IL-2 by continuous intravenous application. During the treatment, NK activity against the NK-sensitive cell line K 562 and against autologous tumor cells was not augmented. However, a significant increase of 2-5A synthetase activity in PBMCs was observed during IL-2 treatment, whereas there was no detectable serum level of IFN-gamma. We conclude that measuring 2-5A synthetase activity in patients treated with IL-2 may be helpful in monitoring the immunomodulatory effects of IL-2 on immune effector cells.
Handgretinger
R
R
Children's University Hospital, Department of Hematology and Oncology, Tuebingen, FRG.
Bruchelt
G
G
Kimmig
A
A
Lang
P
P
Daurer
B
B
Dopfer
R
R
Treuner
J
J
Niethammer
D
D
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood*; D000328:Adult; D002478:Cells, Cultured; D002675:Child, Preschool; D002860:Chromium Radioisotopes; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology; D009447:Neuroblastoma / Q000188:drug therapy / Q000201:enzymology; D011994:Recombinant Proteins / Q000627:therapeutic use
D002860:Chromium Radioisotopes; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase