Characterization of immune development of fetal and early-life of minipigs.

ABSTRACT

Fetal and child's immune systems differ from those of adults. Developing immune systems exhibit increased or decreased sensitivity to drugs, infection, or toxicants compared to adult immune systems. Understanding fetal and neonatal immune systems will help predict toxicity or the pathogenesis or prognosis of diseases. In this study, we evaluated whether the innate and adaptive immune system of fetal and young minipigs could respond to external stimuli compared to a medium-treated group and analyzed several immunological parameters for developmental immunotoxicity according to developmental stages. We performed a hematological analysis of fetal cord bloods and the bloods of neonatal and 4-week-old piglets. Splenocytes were isolated at each developmental stage and treated with lipopolysaccharide (LPS), R848, and concanavalin A (ConA). Various cytokines were measured in the cell supernatants. Total antibody production was also evaluated in serum. The percentage of lymphocytes was dominant in gestational weeks (GW) 10 and 12 and started to decrease from postnatal day (PND) 0. From PND0, the percentage of neutrophils increased. Interleukin (IL)-1ß, IL-6, and interferon (IFN)-α were induced from GW10 in response to LPS and R848 stimulation. Th1 cytokine induction was detected from PND0 upon ConA stimulation, whereas Th2 cytokine release was observed from GW10. IgM and IgG production was sustained at low levels at fetal stages and was significantly increased after birth. This study reconfirmed that the fetal immune system could respond to external stimuli and that hematological analysis, cytokine evaluation, and antibody subclass measurement can be useful parameters for developmental immunotoxicity using minipigs.