Stress response and activity of the hypothalamus-pituitary-interrenal axis (HPI axis) in carp lines with different susceptibility to disease

The stress response is one of the best examples of neuroendocrine-immune interactions. Analogue to the HPA axis in mammals, the stress response in fish is characterized by activation the hypothalamo-pituitary-interrenal (HPI) axis, activation of which starts in the hypothalamic nucleus preopticus (NPO) releasing corticotropic releasing hormone (CRH). CRH stimulates the pituitary to release adrenocorticotropic hormone (ACTH) which is cleaved from pro-opiomelanocortin (POMC). ACTH stimulates release of cortisol from the head kidney. Interestingly, also the crucial pro-inflammatory cytokine IL-1b is involved in both immune and endocrine signalling during stress. Like in mammals, fish leukocytes express receptors for cortisol (GR) and effects of cortisol on the fish immune system generally comply with findings in mammals. This implies that a differential sensitivity to stress may influence the immune response and as a consequence survival. Therefore we studied the stress response in different carp lines that display a differential pathogen susceptibility (R3xR8 and R3 carp are susceptible to bacterial and parasite infection, while R2 and K are relatively resistant). After a stress paradigm of prolonged restraining glucose and cortisol levels were determined, as well as expression of genes involved in HPI axis activity. Stress induced significant increase of serum cortisol levels in all fish lines studied. Both basal and stress-stimulated cortisol levels were higher in the R3xR8 line than in R2, K and R3 fish. In R3 fish we observed stress-induced up-regulation of POMC and GR2 gene expression in the NPO, while in K fish restraining stress slightly down-regulated expression of POMC and GR genes both in NPO and pituitary. Furthermore, both in NPO and pituitary of R3 fish the highest up-regulation of IL- 1b gene expression was observed. Although we are aware of the complexity of the network of connections between stress and susceptibility to pathogens it is striking that the fish more susceptible to infection also exhibit a higher expression of stress related genes.