Interleukin-4 prevents spontaneous in-vitro apoptosis in chronic lymphatic leukaemia but sensitizes B-CLL cells to melphalan cytotoxicity.
The effect of IL4 on cell viability, cell growth, apoptotic fraction, melphalan-induced cytotoxicity and the degree of interstrand DNA cross-linking after alkylating agent exposure was investigated in peripheral blood B-cell chronic lymphocytic leukaemia (B-CLL) cells obtained from 10 patients suffering from chronic lymphocytic leukaemia and in B lymphocytes from five normal individuals. The addition of IL4 to culture medium maintained in-vitro viability and decreased spontaneous in-vitro apoptosis in both B-CLL cells and normal peripheral blood B lymphocytes. IL4 did not, however, stimulate proliferation of either cell type. IL4 sensitized alkylator-resistant B-CLL cells to the cytotoxic effects of melphalan (L-phenylalanine mustard) but had no influence on melphalan-induced cytotoxicity against normal B lymphocytes. The enhanced cytotoxicity against B-CLL cells was accompanied by an increase in the amount of interstrand-DNA cross-linking in these cells following short-term exposure to melphalan.
Pu
Q Q
QQ
Department of Medicine, University of Witwatersrand, Johannesburg, South Africa.
Bezwoda
W R
WR
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008297:Male; D008558:Melphalan / Q000633:toxicity*; D008875:Middle Aged
D018906:Antineoplastic Agents, Alkylating; D015847:Interleukin-4; D008558:Melphalan