Cytokines and intracellular signals involved in the regulation of B-CLL proliferation.
Cytokines play an important role in the regulation of both normal and malignant B cells. In this paper we give a brief overview of the major cytokines involved in the regulation of B-CLL proliferation. In vitro experiments have indicated that there is an antagonistic interaction between TNF-alpha as a growth-enhancing factor and IL-4, which inhibits the growth of B-CLL. We have extended these findings with recent experiments on the intracellular signals which might be involved in these processes. We show that increased levels of intracellular cAMP dose-dependently inhibit the TNF-alpha-induced proliferation of B-CLL. On the basis of these results, we propose a model for the signals involved in the regulation of B-CLL proliferation. The implications for possible new ways of treatment are discussed.
van Kooten
C
C
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
Rensink
I
I
Aarden
L
L
van Oers
R
R
D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D015398:Signal Transduction; D014178:Translocation, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4