Cytokine Profiles in Infants with Congenital Cytomegalovirus (CMV) Infection† 814

Abstract

CD4+ T lymphocytes comprise functionally heterogeneous populations with specific profiles of cytokine production. Th1 cells produce IL-2, IFN-γ and TNF-β, whereas Th2 cells produce IL-4, IL-5, and IL-10. To characterize the cytokine responses in intrauterine CMV infection, we investigated the cytokine production by PBL in response to polyclonal and antigenic responses. Production of IFN-γ, IL-2, IL-4 and IL-10 was measured in cultures of PBL from 15 children with congenital CMV infection (7 with symptoamtic and 8 with asymptoamtic infection) and 8 healthy neonates(controls) within the first 2 months of life using cytoscreen ELISA kits(Biosource International, Camarillo, CA). The results cytokine levels(mean±1 SD) are shown in the table below. Unstimulated cultures and those stimulated with the major envelope glycoprotein B (gB) of CMV produced similar levels of cytokines in both groups. Upon stimulation with phytohemagglutinin (PHA) plus phorbol-12-myristate-13-acetate (PMA), infants with congenital CMV infection produced less IFN-γ than control children (p<.01). Although PBL from infants with symptomatic congenital CMV infection produced lower amounts of IFN-γ than those with asymptomatic infection, the difference was not statistically significant (p=.08). Furthermore, the group of infants with symptomatic infection produced increased amounts of IL-10 in cultures than asymptomatic infants and the control group and the difference approached statistical significance (p=.055). The levels of IL-2 and IL-4 were not different between the congenitally infected infants and the control subjects. The results suggest that infants with congenital CMV infection exhibit decreased production of mitogen stimulated Th1 type cytokines and increased TH2 cytokines (IL-10). Although the significance of these findings is not entirely clear, the differences in cytokine response may explain the decreased or absent cell mediated immune responses to CMV antigens observed in most infants with congenital CMV infection. The patterns of cytokine expression is being investigated in the study children.