Time-dependent effect of inflammation on the gene expression of pro-inflammatory cytokines and their receptors at the different levels of the somatotropic axis in ewe

Abstract

. Pituitary-hypothalamic-somatotropic (HPS) axis plays a key regulatory role in the metabolic and physiological processes in mammals. It is considered that inflammatory mediators such as proinflammatory cytokines, whose receptors are widespread at the different levels of the HPS axis, may be responsible for disturbing this axis activity. Our study was carried out to determine the effect of lipopolysaccharide (LPS)-induced inflammation on the expression of genes encoding pro-inflammatory cytokines and their receptors in the organs belonging to the HPS axis. In vivo studies were carried out on ewes (n = 36) divided randomly into 3 time-dependent groups (n = 12; each). Each time group was divided into two subgroups: control (saline-treated; n = 6) and intravenously treated with LPS (400 ng/kg; n = 6). Animals were euthanized 1.5 h, 3 h, or 9 h after LPS injection; and the fragments of the dorsomedial hypothalamus and mediobasal hypothalamus, anterior pituitary, and liver were collected. The relative gene expression encoding IL1B, IL1R1, IL1R2, IL6, IL6R, IL6ST, TNF, TNFRSF1A, and TNFRSF1B was determined with real-time PCR. Our experiment showed that LPS-induced inflammation modulates the gene expression of pro-inflammatory cytokines such as IL1B , IL6 , and TNF and their corresponding receptor at the different levels of the HPS axis in sheep at the time-dependent manner. Because these cytokines are known as potent modulators of the secretion of hormones and neurohormones, the paracrine action of these locally synthesized cytokines may disturb the activity of the HPS axis; however, it requires further deep-in research.