Comparative cytokine production by in vitro stimulated mononucleated cells from cord blood and adult blood.

Cord blood transplantations successfully reconstituted hemopoiesis in patients treated with myeloablative therapies. These transplantations were associated with a low rate of acute graft-versus-host disease (aGVHD), a major life-threatening complication of allo-transplantation. The physiopathology of aGVHD implies the recognition of host alloantigens by donor T cells but also involves a cytokine cascade. In this cascade, interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) produced by donor T cells and monocytes/macrophages play a major effector role. Therefore, we investigated whether the lower percentage of aGVHD in cord blood transplants could be related to a lower ability to produce these cytokines in vitro compared with adult blood. Mononucleated cells (MNCs) isolated from term cord blood and adult peripheral blood were stimulated with a combination of lipopolysaccharide and phytohemaglutinin and incubated for 96 hours. Levels of IL-1beta, IL-2, IL-3, IL-4, IL-6, TNF-alpha, IFN-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in the supernatants after various times of incubation. The productions of IL-1beta, IL-6, and GM-CSF were similar in stimulated cord and adult blood and IL-3 levels, though lower and delayed in cord blood, were not statistically different. On the other hand, we found markedly lower levels of IFN-gamma, TNF-alpha, and IL-4 in cord blood throughout the incubation period. The stimulated levels of IL-2 were similar in cord and adult samples throughout the first 48 hours of incubation but became significantly lower in cord blood after 72 and 96 hours. We suggest that the cytokine production pattern that characterizes cord blood could provide an explanation for the lower occurence of aGVHD following cord blood transplants.