Kinetics of restoration of interferon production after bone marrow transplantation in man.
Peripheral blood mononuclear cells (PBMC) from 21 patients after bone marrow transplantation (BMT) were studied for their capacity to produce interferon (IFN) in vitro. The basal and IFN-stimulated 2-5 A synthetase activity was also investigated as a marker of the cells' ability to respond to exogenous IFN. All but one patients received cyclosporin A as a prophylaxis against graft-versus-host disease (GVHD). GVHD was diagnosed in three patients. IFN production in response to stimulation with phytohemagglutinin or poly I:C was not detectable in most patients without GVHD until 7 months after grafting. However, in a proportion of recipients without GVHD, studied early after BMT, transient normal IFN production was observed. In contrast to patients without GVHD, PBMC from patients with GVHD produced stable high levels of IFN when stimulated in vitro. The impairment of IFN production did not correlate with conditioning regimens, infection, plasma cyclosporin levels or the lymphocytes' blastogenic response to the mitogens. Addition of interleukin-2 (IL-2) to culture medium of fresh unresponsive PBMC restored only partially the defective IFN production. Similarly, T-cell lines propagated in IL-2 conditioned medium, from unresponsive PBMC, produced low levels of IFN gamma when stimulated with PHA. The basal activity of 2-5 A synthetase in PBMC from patients without GVHD could not be stimulated, during the first 3 months after BMT, by the cultivation of cells with IFN alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
Koscielniak
E
E
Department of Hematology, Children's Hospital, Tübingen, GFR.
Bruchelt
G
G
Treuner
J
J
Uchanska-Ziegler
B
B
Dopfer
R
R
Vallbracht
A
A
Niethammer
D
D
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D003524:Cyclosporins / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007372:Interferons / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011184:Postoperative Period; D013997:Time Factors
D003524:Cyclosporins; D007369:Interferon Inducers; D007376:Interleukin-2; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase