Modulation of cell proliferation and cytokine production in AML by recombinant interleukin-1 receptor antagonist
| Autor: | Rambaldi, A., Maria Torcia, Dinarello, Ca, Barbui, T., Federico Cozzolino |
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| Rok vydání: | 1993 |
| Předmět: | |
| Zdroj: | Europe PubMed Central Scopus-Elsevier Università degli studi di Firenze-IRIS |
| ISSN: | 0887-6924 |
| Popis: | In Acute Myelogenous Leukemia (AML), Interleukin 1 (IL-1) might sustain autocrine and paracrine loops of leukemic growth. An IL-1 inhibitor has been recently purified and cloned. This molecule binds to the IL-1 receptors but has no IL-1 like activity fulfilling the characteristics of a pure Interleukin-1 receptor antagonist (IL-1ra). We studied the in vitro effect of human recombinant IL-1ra on proliferation of AML blasts. Spontaneous as well as IL-1 stimulated AML proliferation was significantly inhibited by the addition of 50 ng/ml of recombinant IL-1ra in a dose dependent manner. The inhibitory effect of IL-1ra was measurable after 12 hours of culture and reached a plateau at 60 hrs. We found that IL-1ra could compete with IL-1 in binding to specific IL-1 receptors on AML cells. As expected, culture supernatants of unstimulated leukemic samples contained IL-1 beta and GM-CSF activity. The incubation of the same leukemic blasts with IL-1 ra was followed by reduction or disappearance of GM-CSF in culture supernatants whereas the IL-1 beta production was only partially modulated. By Northern blot experiments performed on freshly isolated, uncultured leukemic blasts, we found a constitutive expression of the IL-1 beta gene in 19 of 23 AML cases analyzed. On the contrary, only three of these patients express the IL-1 RA mRNA. All together these results suggest that imbalanced secretion of IL-1 and its natural receptor antagonist could contribute to the unrestricted growth of AML cells. |
| Databáze: | OpenAIRE |
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