Immunoregulatory cytokines in bone marrow and peripheral blood stem cell products.

Abstract

In these studies, we compared the phenotype, function, and expression of type 1, type 2, and monocyte-associated cytokine mRNA transcripts in autologous bone marrow (BM) and growth factor-mobilized peripheral blood stem cell (PSC) products. These studies demonstrate that lymphocytes and monocytes in stem cell products are abnormally activated, expressing significantly higher levels of interleukin (IL)-2, 4 and 10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), but not IL-8, as compared to normal peripheral blood mononuclear cells (PBMC). In addition, the levels of IL-2, IL-10 and TNF-alpha are significantly higher in mobilized PSC as compared to BM products. The high cytokine levels are unexpected as T cell function in stem cell products is depressed. PSC products have high levels of T cell inhibitory activity, which directly correlates with IL-10 expression, both of which are mechanisms that might be involved in the immune dysfunction within stem cell products used for autologous stem cell transplantation. These data demonstrate that: (1) immune cells in autologous BM and PSC products are activated with the expression of high levels of type 1 and type 2 cytokines as well as monokines; (2) PSC products contain a high frequency of monocytes which mediate T cell inhibitory activity; and (3) despite the high levels of cytokine expression, T cell function in stem cell products is depressed. The significance of these immune abnormalities within stem cell products for myeloid and lymphoid recovery following autologous stem cell transplantation remains to be determined.