Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals

Abstract

Neonates are thought to be generally deficient in production of Th-1-associated cytokines at birth, and thereby more susceptible to bacterial infections. Using neonatal foals as a model, this study examined the age-dependent maturation of both basal and stimulus-induced immune responses, as reflected by the expression of a panel of Th-1-associated and pro-inflammatory cytokines. Results showed that although the basal production of IFN-gamma and IL-6 was impaired (P<0.05) in PBMCs of neonatal foals at birth, the basal production of IL-8, IL-12(p35/p40) and IL-23(p19/p40) were either in excess of or comparable to that of older foals. In response to Rhodococcus equi and CpG-ODN stimulation in vitro, PBMCs of neonatal foals showed increased (P<0.05) expression of IFN-gamma and IL-6, and preferentially increased expression of either IL-23(p19/p40) with R. equi stimulation or IL-12(p35/p40) with CpG-ODN stimulation. The magnitude of these stimulus-induced responses (except for IL-23p19), were significantly (P<0.05) less for newborn foals than for older foals. The selective impairment of age-dependent basal and stimulus-induced cytokine expression by newborn foals may reflect the different functional state of various TLR pathways in newborns, and be directly associated with their age-dependent susceptibility to infection. Our results indicate that CpG-ODNs can selectively stimulate deficient cytokines (P<0.05) from PBMCs in newborn foals in vitro, suggesting immunoprophylactic or therapeutic potential of CpG-ODNs.