Preferential release of high amounts of interleukin-8 by myeloid blasts showing monocytic differentiation

Abstract

BACKGROUND. In myeloid blasts, the expression and release of the multifunctional chemokine IL-8 could be expected to be differentiation-associated. METHODS. We investigated the profile of interleukin-8 (IL-8) expression and release by leukemic cells obtained at diagnosis from 42 untreated adult patients with acute myeloid leukemia of various FAB subtypes (2 M0, 7 M1, 6 M2, 6 M3, 10 M4 and 11 M5). IL-8 transcripts were evaluated by Northern blot and densitometric analysis. IL-8 release by myeloid blasts was evaluated by a specific ELISA either in sera at diagnosis or in supernatants (SN) obtained from cultured leukemic cells. RESULTS. In basal conditions, Northern blot analysis revealed detectable IL-8 transcripts in 15/29 cases, eleven of which were classified as M4-M5 and 4 as FAB M0-M3. Densitometric analysis of IL-8 transcript bands showed higher expression in M4-M5 than in M0-M3 cases (mean values +/- SD: 16.5 +/- 21 and 0.77 +/- 1.36 densitometric units, respectively; p = 0.012). Higher IL-8 serum levels were observed in leukemic patients as opposed to normal controls (mean values +/- SD: 0.53 +/- 0.75 vs 0.003 +/- 0.014 ng/mL, respectively; p = 0.006). Furthermore, a trend (though not of statistical significance) towards higher IL-8 serum values was observed in M4-M5 as opposed to M0-M3 subtypes. After 24 hours of culture, the majority of myeloid blasts (95%) spontaneously released detectable amounts of IL-8 into SN. However, M4-M5 released substantially higher amounts of IL-8 than M0-M3 blasts (mean +/- SD: 68 +/- 46 and 8.5 +/- 12 ng/mL, respectively; p < 0.001). This difference between M0-M3 and M4-M5 blasts was already observed after 6 hours of culture and increased over 72 hours. CONCLUSIONS. Our findings confirm and further support the preferential release of high levels of IL-8 by myeloid blasts showing monocytic differentiation.