ABSTRACT
OBJECTIVE: Since perinatal stress events are well known to exert long-term influences on the function of hypothalamic-pituitary-adrenal (HPA) axis in rats, to investigate the consequences of exposure to IL-1, a potent stimulator of this axis, during early postnatal life. METHODS: Wistar rats were treated twice a day with 0.02 ug human recombinant IL-1 from day 1-4 of age, while controls received the vehicle only. RESULTS: IL-1 -treatment had no significant influence on the mortality and body weight. However, at the end of treatment period on the 4th day of life, the thymus weight was decreased in the IL-1 -treated group (P<0.01), while the adrenals were clearly enlarged (P<0.0002). These responses were associated with a nearly 4-fold elevation of the plasma corticosterone (CS) level as compared to vehicle-treated controls (P<0.001). At the age of seven months the stimulated CS levels induced by an acute stress (novel environment) were lower in rats treated neonatally with IL-1 than in controls (P<0.01). This functional disturbance was associated with morphological alterations in the parvicellular part of the paraventricular nucleus (PVN) which is the main hypothalamic regulation centre of the HPA axis. A strong reduction of the numerical density of neurons was found in the neonatally IL-1 -treated rats (P<0.005) while the neuronal nuclei were clearly enlarged (P<0.0005). CONCLUSION: As a part of an infection-induced stress response during critical periods of development, IL-1 might be capable of inducing a permanent structural malorganization of the PVN and, consequently, functional malprogramming of the HPA axis in rats.
ABSTRACT
Nervous, endocrine and immune systems are regarded as a complex functional unit, interacting by their specific chemical messengers-neurotransmitters, systemic hormones and hormone-like mediators of immune cells (cytokines). Cytokines are known to affect several endocrine axes. Interleukin-1 beta (IL) was administered in rats intraperitoneally twice daily from day 17 to 21 of pregnancy. Some of the IL-treated mothers were rapidly decapitated 1.5 h after the last injection. The fetuses were delivered by cesarean section. Maternal plasma CRF, ACTH and corticosterone were found to be significantly elevated. Fetal adrenal and thymus weights were lower, and plasma corticosterone did not differ from controls. Fetal plasma testosterone was decreased in males, androstenedione was increased in females. Open-field testing revealed a higher total locomotor activity of IL offspring than of controls. IL offspring showed worse results in Skinner box learning than controls. Sexual behavior was only affected in males, showing a higher percentage of female-type lordosis behavior after castration and estrogen treatment compared to controls. At the age of 6 months responsiveness to 'novel-environment stress' of IL groups was significantly lower than that of controls in terms of plasma corticosterone. These results indicate that prenatal treatment with IL-1 beta results in long-lasting alterations in psychomotor development, behavior as well as in the neuroendocrine system.
