Severe stress such as immobilization (IMO) affects the central nervous system,the endocrine system and the immune system that interact each other.IMO-induced responses are activation of hypothalamic-pituitary-adrenal (HPA) axis and production of inflammatory cytokine.The locus coeruleus (LC),which is known to play a role in modulating stress response,innervates the paraventricular neucleus (PVN) of the hypothalamus thereby activating HPA-axis.In this study,IMO-induced alterations of HPA-axis hormones and interleukin-4 (IL-4) were investigated.Also,IL-4 secreting cells in the LC were examined.The final hormone of HPA-axis,corticosterone (CORT) was injected to clarify the interaction of the HPA-axis and IL-4 in the stress response.Single exposure of stress resulted in an increase of corticotrophin-releasing factor expression in the PVN,adrenocorticotropin hormone and CORT levels in the serum.Increased expressions of HPA-axis hormones in the acute stressed group were decreased in repeated stressed group.IL-4 level in the LC of the brain was decreased in both stressed group and repeated CORT injected group.IL-4 secreting cells were co-localized with tyrosine hydroxylase-producing cells in the LC.These results suggest the possibility of stress-induced interplay of HPA-axis and IL-4 in the noradrenergic neurons of the LC.