Modulatory Role of the Epinergic System in the Neuroendocrine-Immune System Function

Abstract

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 (TNFα) concentrations were enhanced severalfold (p < 0.05 vs. basal values) after LPS treatment in CTRL rats, but not in SKFs-treated animals. In order to explore the reduced cytokine release after LPS in PNMT-inhibited rats, additional ex vivo experiments were performed by using peripheral mononuclear cells (PMNC) from both CTRL and SKF-29661-pretreated rats. The results of these experiments confirmed an immune dysfunction after inhibition of peripheral EPI synthesis; in fact, basal and concanavalin-A-stimulated TNFα secretions were significantly (p < 0.05) lower in SKF-29661-treated than in CTRL PMNC, while, interestingly, addition of ...

Neuroimmune Regulation in Immunocompetence, Acute Illness, and Healing

“…An inhibitor of central EP synthesis (SKF 64139) enhanced basal medial hypothalamus (BMH) and basal median eminence (BME) VP contents in adult male rats. LPS administration significantly decreased BMH VP in control and peripheral EP inhibitor (SKF 29661)‐pretreated rats and diminished BME VP in all groups 128 …”

Sympathetic innervation of the spleen in male Brown Norway rats: A longitudinal aging study

“…First, physical and psychosocial stressors can affect an immune function by elevating circulating stress hormones [Szelenyi and Vizi, 2007; Starkie et al, 2005; Moncek et al, 2003; Giovambattista et al, 2000; Condé et al, 1999; Hasko et al, 1995; Mujika et al, 2004; Brenner et al, 1998; Pederson et al, 1997; Pyne, 1994; Hinrichsen et al, 1992]. Second, exposure to environmental antigens is in and of itself a stressor, affecting the reactivity of the SNS and SAM (Sakata et al, 1994; Moncek et al, 2003; Giovambattista et al, 2000). …”

Modulatory Role of the Ovarian Function in Neuroimmunoendocrine Axis Activity

“…This method is similar to the one previously described with minor modifications [33] . Heparinized blood was collected by heart puncture (under light ether anesthesia) from sham-operated and ovariectomized mice.…”

“…Leptin circulating levels and medium concentration were measured by a previously reported and validated specific radioimmunoassays developed in our laboratory [34] ; the intra-assay and inter-assay coefficients of variation ranged between 5-8 and 10-13%, respectively. The assay for TNF ␣ was that based on the cytolytic effect of this cytokine on cultured L929 cells, as previously described and validated in our laboratories [33] ; with TNF ␣ used as standard. Cells were maintained in MEM containing 10% (v/v) of fetal calf serum, glutamine and antibiotics (pH 7.4).…”