The effect of cytokines on cultured mononuclear cells from patients with B cell chronic lymphocytic leukemia.
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-alpha, IFN-gamma, 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 [3H]-thymidine without going into mitosis. The majority of cultures produced biologically active TNF at levels ranging from 1 to 40 pg/ml. In IFN-alpha 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-1 beta 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-1 beta mRNA were detected in a minority of mononuclear cells.
Burke
F
F
Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London, U.K.
Griffin
D
D
Elwood
N
N
Davis
C
C
Stamp
G
G
Rohatiner
A
A
Lister
T A
TA
Balkwill
F
F
D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D015152:Blotting, Northern; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012334:RNA, Neoplasm / Q000032:analysis; D013936:Thymidine / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D016207:Cytokines; D004273:DNA, Neoplasm; D015850:Interleukin-6; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D013936:Thymidine