ABSTRACT
When considering the immune system, it is possible that the differential risk may be the result of differences in three aspects of the dose-response curve for any agent. It is possible that a chemical may be toxic only to the developing immune system (Fig. 18.1A), due to some unique property of the developmental window targeted, the agent tested, or both. To date, we have not identified developmental immunotoxicants that are not also immunomodulatory in the adult; however, this may be a function of the state of the-science and the availability of this information in published forms. What has more typically been observed with chemicals is that either the immunologic doseresponse curve to the agent is shifted to the left in younger animals (Fig. 18.1B), or that while the dose-response curves may be similar, the effects observed in the young persist longer even after the exposure to the agent ceases (Fig. 18.1C). In at least one case (diethylstilbestrol in mice), this persistence was observed to continue for 6-17 months following neonatal (postnatal day [PND] 1-5) exposure (20-23). Indeed, the literature in recent years is filled with examples suggesting that the developing immune system is more sensitive than that of the adult for some immunotoxic alterations (23,24). This apparent sensitivity may be due, in large part, to the novel immune maturation events that include the need for rapid perinatal changes in functional balance to restore the critical immune balance between Th1 and Th2 (alternative responses by the body’s T-helper cells) through the enhancement of Th1 capacity in the newborn (25,26).
