Clinico-biological implications of increased serum levels of interleukin-8 in B-cell chronic lymphocytic leukemia.
OBJECTIVE
Constitutive cellular expression and serum release of biologically active interleukin-8 (IL-8) has been reported in B-cell chronic lymphocytic leukemia (CLL). Given the autocrine role played by IL-8 in the process of cell accumulation characteristic of this disease we tried to investigate clinico-biological implications of increased serum levels of this cytokine in an unselected series of B-cell CLL patients.


METHODS
Serum levels of IL-8 were determined at the time of diagnosis in 58 previously untreated B-CLL patients using an immunoenzyme assay. Results were correlated with main clinico-hematologic features as well as with the risk of disease progression. Finally, we looked for associations between IL-8 and molecules directly involved in apoptosis, such as intracellular bcl-2 and soluble APO-1/Fas.


RESULTS
Increased serum levels of IL-8 were found in 15 out of 58 (25.8%) B-cell CLL patients. Serum levels of IL-8 did not reflect clinico-biological features representative of tumor mass such as clinical stage, histopathologic pattern of bone marrow (BM) involvement, b2-microglobulin, sCD23 and sCD27 titers. Interestingly, circulating levels of IL-8 paralleled those of intracellular bcl-2 (r = 0.522; p = 0.01), thus confirming that the antiapoptotic effect of IL-8 can be exerted through a bcl-2 dependent pathway. Levels of IL-8 did not match those of soluble Apo-1/Fas (r = -0.013; p = 0.943). Finally, stage A patients with levels of IL-8 above the median value (i.e. 4.5 pg/mL) were more likely to progress to a more advanced clinical stage than those with levels below the median value (p < 0.05).


CONCLUSIONS
IL-8 is an interesting marker in B-cell CLL, closely involved in the pathogenesis of disease. Furthermore, it is useful for predicting the pace of disease progression in early clinical stages.
Molica
S
S
Divisione Ematologia, Azienda Ospedaliera "Pugliese-Ciaccio", viale Pio X, 88100 Catanzaro, Italy.
Vitelli
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G
Levato
D
D
Levato
L
L
Dattilo
A
A
Gandolfo
G M
GM
D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood*; D001853:Bone Marrow / Q000473:pathology; D018450:Disease Progression; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D016209:Interleukin-8 / Q000097:blood* / Q000502:physiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood* / Q000502:physiology; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D017455:Receptors, IgE / Q000097:blood; D012307:Risk Factors; D001613:beta 2-Microglobulin / Q000032:analysis
D014408:Biomarkers, Tumor; D016209:Interleukin-8; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017455:Receptors, IgE; D001613:beta 2-Microglobulin