Interleukin-4 (IL-4), but not IL-10, regulates the synthesis of IL-6, IL-8and leukemia inhibitory factor by human bone marrow stromal cells

Leukemia inhibitory factor (LIF), interleukin 6 (IL-6) and IL-8 are importa nt regulators of inflammation and hematopoiesis. Human bone marrow stromal cells regulate marrow hematopoiesis by secreting cytokines. By using revers e-transcriptase polymerase chain reaction (RT-PCR), we demonstrate that hum an bone marrow stromal cells constitutively express LIF, IL-6 and IL-8 tran scripts. By using specific ELISAs, we found that their spontaneous producti ons of LIF, IL-6 and IL-8 are elevated in response to serum and after stimu lation with the pro-inflammatory cytokines IL-1 alpha and TNF-alpha. The an ti-inflammatory cytokine IL-4 reduces their serum- and cytokine-induced LIF secretion. By contrast, IL-4 stimulates their serum- and IL-1 alpha-induce d IL-6 synthesis. IL-4 has no effect on the serum-induced IL-8 synthesis by marrow stromal cells, but stimulates their cytokine-induced IL-8 productio n. The anti-inflammatory cytokine IL-10 has no effect on the serum- and cyt okine-induced LIF, IL-6 and IL-8 synthesis by bone marrow stromal cells. RT -PCR experiments reveal the presence of IL-4 receptor alpha-chain mRNA and IL-10 receptor mRNA in cultured bone marrow stromal cells. The differential regulation by IL-4 of two related cytokines, such as LIF and IL-6, and the enhanced effect of this 'anti-inflammatory' cytokine on IL-6 and IL-8 synt hesis highlight the tightly controlled regulation and the complexity of the cytokine production within the human bone marrow. (C) 1999 Elsevier Scienc e B.V. All rights reserved.