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The effect of cytokines on cultured mononuclear cells from patients with B cell chronic lymphocytic leukemia
Author(s) -
Burke Frances,
Griffin Dorota,
Elwood Nagaire,
Davis Carol,
Stamp Gordon,
Rohatiner Anna,
Lister T. Andrew,
Balkwill Frances
Publication year - 1993
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2900110104
Subject(s) - peripheral blood mononuclear cell , chronic lymphocytic leukemia , immunology , leukemia , medicine , cancer research , biology , in vitro , biochemistry
Abstract In the past 5 years a number of cytokines have been identified that control B cell development, proliferation, and maturation. The role of such cytokines in the evolution, pathophysiology, and treatment of B cell malignancies is an area of great interest. The in vitro response of freshly isolated peripheral blood mononuclear cells from patients with B cell chronic lymphocytic leukemia (B‐CLL) and a high white cell count, to four cytokines, IFN‐α, IFN‐γ, IL‐2 and TNF, was studied. No culture condition or cytokine resulted in a significant increase in cell number over 4 days, cells survived better in autologous serum than in heat inactivated foetal calf serum, and a small but significant increase in blast cells was seen when the cells were cultured in IL‐2. There was a discrepancy between uptake of thymidine and increase in cell number which can be explained by the low labelling index of these cultures and the fact that cells can incorporate [ 3 H]‐thymidine without going into mitosis. The majority of cultures produced biologically active TNF at levels ranging from 1 to 40 pg/ml. In IFN‐α treated cultures TNF levels were decreased. Cultures contained biologically active IL‐6 at levels ranging from 2 to 2800 U/ml. IL‐6 production was not influenced by other cytokines. Thirteen of 28 patients had detectable IL‐6 in their serum, but in cells lysed no more than 2 h after removal from the patient, message for IL‐6 could not be detected by Northern blotting. Cells also failed to express IL‐1β mRNA but seven of eight patients had low levels of TNF message. Preliminary data using in situ hybridization techniques revealed that whilst no mRNA for IL‐6 was detected, TNF and IL‐1β mRNA were detected in a minoority of mononuclear cells.