pituitrin and Acute-Phase-Reaction

It is well recognized that the reciprocal interaction established between the immune and neuroendocrine systems is crucial for the homeostatic adaptation of individuals during septicemia. In the present study, using an in vivo rat model, we investigated the degree of participation of central and peripheral epinergic systems in the modulation of the hypothalamic-pituitary-adrenal and immune axes' functions during endotoxemia. For this purpose, acute endotoxemia was induced in adult male rats pretreated intraperitoneally with either different inhibitors of phenylethanolamine-N-methyltransferase (PNMT) [which are active either peripherally (SKF 29661) or both peripherally and centrally (SKF 64139), thus lowering epinephrine (EPI) synthesis] or vehicle only (CTRL). Twelve hours after pretreatment, animals were intraperitoneally injected with vehicle alone (basal) or vehicle containing bacterial lipopolysaccharide (LPS) and sacrificed 2 h later. A significant (p < 0.05 vs. the respective basal value) hypoglycemia was found in all groups studied. No pretreatment modified basal plasma adrenocorticotropic hormone (ACTH), glucocorticoid and cytokine concentrations. Endotoxin-stimulated ACTH secretion was severalfold (p < 0.05) higher than the respective basal value in CTRL and in SKFs-pretreated rats; however, the plasma ACTH levels after LPS were significantly (p < 0.05 vs. CTRL and SKF-29661 values) reduced in SKF-64139-pretreated rats. All groups studied showed an appropriate adrenal response to endotoxin challenge. Although no differences were found in basal anterior pituitary (AP) ACTH content among groups, LPS treatment significantly (p < 0.05 versus the respective basal value) decreased AP ACTH in CTRL and SKF 29661 groups. No pretreatment modified the basal medial basal hypothalamus (MBH) corticotropin-releasing hormone (CRH) content. Conversely, SKF 64139 pretreatment significantly (p < 0.05 vs. CTRL and SKF 29661 values) reduced basal median eminence (ME) CRH content, and LPS administration significantly (p < 0.05) decreased ME CRH in CTRL and SKF-29661-pretreated rats. SKF 64139 pretreatment significantly (p < 0.05) enhanced basal MBH and ME arginine vasopressin (AVP) contents. LPS administration significantly (p < 0.05) decreased MBH AVP in CTRL and SKF-29661-pretreated rats and diminished (p < 0.05 vs. basal values) ME AVP in all groups. The plasma tumor necrosis factor alpha (TNFalpha) concentrations were enhanced severalfold (p < 0.05 vs. basal valu

Topics: Acute-Phase Reaction; Adrenocorticotropic Hormone; Animals; Corticotropin-Releasing Hormone; Enzyme Inhibitors; Epinephrine; Hypoglycemia; Hypothalamo-Hypophyseal System; Isoquinolines; Lipopolysaccharides; Male; Neuroimmunomodulation; Norepinephrine; Phenylethanolamine N-Methyltransferase; Pituitary-Adrenal System; Rats; Rats, Inbred F344; Tetrahydroisoquinolines; Tumor Necrosis Factor-alpha; Vasopressins

Immature (3 week old) rat offspring of alcohol (E)-fed dams show a blunted ACTH response to immune signals such as interleukin-1 beta (IL-1 beta) and endotoxin (LPS). In contrast, mature offspring respond to physical stresses with an exaggerated activation of their hypothalamic-pituitary-adrenal (HPA) axis. The present work was aimed at determining if there was a differential influence of prenatal E exposure on the HPA axis responses to various stressors or if, alternatively, sexual maturation modified these responses. When administered IL-1 beta at 5 weeks age, E-treated intact male offspring released less ACTH, compared to control (C) or pair-fed (PF) animals. However, they showed an augmented response to LPS and a local inflammatory process induced by turpentine injection. At this same age, intact E females secreted significantly more ACTH in response to IL-1 beta, LPS and turpentine, than C or PF offspring. By 9 weeks of age, both E males and E females exhibited larger (p < .05) ACTH responses to all three immune stimuli. In order to determine whether sex steroids modulate the influence of E in females, ovariectomy was done prior to puberty. This treatment decreased the difference in the ACTH released by E and C rats in response to IL-1 beta, LPS and turpentine. These results show that while immature rats exposed to E prenatally released less ACTH in response to cytokines than C or PF animals did, this response was qualitatively reversed after puberty. At that time, the larger amounts of ACTH secreted by E offspring, compared to the other groups, were reminiscent of the hyperactive response of the HPA axis when these offspring were exposed to physical stress. Interestingly, removal of circulating ovarian steroids prevented the influence of E from being exerted. This suggests the presence of a functional relationship between the pathways influenced by prenatal E and those influenced by female sex steroids, that are important in regulating the activity of the HPA axis.

Topics: Acute-Phase Reaction; Adrenocorticotropic Hormone; Animals; Arousal; Corticosterone; Corticotropin-Releasing Hormone; Cytokines; Female; Fetal Alcohol Spectrum Disorders; Gonadal Steroid Hormones; Hypothalamo-Hypophyseal System; Interleukin-1; Lipopolysaccharides; Male; Pituitary-Adrenal System; Pregnancy; Rats; Rats, Sprague-Dawley; Sex Factors; Sexual Maturation; Vasopressins