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Cytokine gene expression in B-cell chronic lymphocytic leukemia: evidence
of constitutive interleukin-8 (IL-8) mRNA expression and secretion of
biologically active IL-8 protein
PF di Celle, A Carbone, D Marchis, D Zhou, S Sozzani, S Zupo, M Pini, A Mantovani and R Foa
Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione Clinica,
University of Turin, Italy.
To extent our knowledge on the cytokines possibly involved in the
pathophysiology of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA
expression of a panel of 10 cytokines was investigated on purified B-CLL
cells using a reverse-transcriptase polymerase chain reaction method.
Whereas negative RT-PCR signals were recorded for interleukin-1 alpha (IL-1
alpha), IL-2, IL-3, IL-4, IL-5, IL-7, tumor necrosis factor beta (TNF
beta), and granulocyte-macrophage colony-stimulating factor, we detected
the expression of IL-1 beta, IL-6 and TNF alpha. Furthermore, the
constitutive expression of IL-8 mRNA was observed in all 17 B-CLL samples
analyzed. mRNA expression was associated with the capacity of the leukemic
cells to release IL-8 both constitutively (4.6 +/- 8.1 SD ng/mL) and, to a
further extent, after stimulation (14.5 +/- 19.4 ng/mL). The circulating
levels of IL-8 were also evaluated in 12 untreated B-CLL sera samples and
the overall mean level was significantly higher (P < .01) than in normal
sera. In addition, supernatants of purified B-CLL cells cultured in the
presence of 12-O- tetradecanoylphorbol-13-acetate showed chemotactic
activity towards neutrophils; this activity was neutralized in the presence
of an anti- IL-8 antiserum. The mRNA for IL-8 was absent in five B-cell
preparations from hairy cell leukemia cases and in four B-cell lines.
Normal tonsil CD5+ B cells showed a low expression of IL-8 mRNA only in two
of the nine preparations tested and the overall quantity of IL-8 released
by these cells after 3 days' incubation was significantly lower compared
with that released by B-CLL cells (0.4 +/- 0.3 and 1.6 +/- 0.9 ng/mL under
basal and stimulated conditions, respectively). These findings point to an
involvement of a member of the proinflammatory chemokine supergene family
in human CD5+ B lymphocytes. The different IL-8 behavior observed between
B-CLL cells and their normal counterpart is likely to reflect an activation
state of the leukemic population.
Volume 84,
Issue 1,
pp. 220-228,
07/01/1994
Copyright © 1994 by The American Society of Hematology
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