Intracellular cytokine production and cytokine receptor interaction of cord mononuclear cells: relevance to cord blood transplantation

A 'cytokine storm' consisting of IL-1, IL-2, IL-12, IFN gamma and TNF alpha is considered important in the development of graft-versus-host disease (GVHD). These cytokines activate effector cells or damage host tissues. Cord blood transplantation has been associated with a low incidence of GVHD. We hypothesized that the low incidence of GVHD relates to the cord mononuclear cells being poor producers of pro-inflammatory cytokines. The cytokine profile (IL-1 alpha/beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN gamma and TNF alpha) of cord blood cells induced by immune stimuli was determined in heparinized whole blood. Compared to adult, cord blood CD3(+) and NK cells produced less IFN gamma, less cord blood CD3(+) cells and monocytes produced TNF alpha and less monocytes produced IL-1 alpha/beta. Although more cord T cells produced IL-2 compared to adult T cells at 4 h, adult T cells produced more at 24 h. Cord blood had similar proportions of monocytes to adult producing IL-6, IL-10 and IL-12. Both adult and cord mononuclear cells constitutively expressed receptors for IFN gamma and TNF alpha but not IL-12. In contrast to the adult cells, cord CD3(+) and NK cells did not express IL-12 receptor but did up-regulate IL-10 receptor after mitogenic stimulation. The findings of this study indicate that the cord blood cytokine-receptor network is biased towards anti-inflammatory activity compared to adult and helps to explain the decreased incidence of GVHD in cord blood transplantation.