Research Article: Regulation of Intestinal Immune Response by Selective Removal of the Anterior, Posterior, or Entire Pituitary Gland in Trichinella spiralis Infected Golden Hamsters

Date Published: March 15, 2013

Publisher: Public Library of Science

Author(s): Rosalía Hernández-Cervantes, Andrés Quintanar-Stephano, Norma Moreno-Méndoza, Lorena López-Griego, Valeria López-Salazar, Romel Hernández-Bello, Julio César Carrero, Jorge Morales-Montor, Josep Bassaganya-Riera.


The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been previously reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion and intestinal absorption, as well as increased susceptibility to bacterial and viral infections. However, to our knowledge, no findings have been published concerning the immune response following HYPOX during worm infection, particularly that which is caused by the nematode Trichinella spiralis. The aim of this work was to analyze the effects of total or partial HYPOX on colonization of T. spiralis in the intestinal lumen, together with duodenal and splenic cytokine expression. Our results indicate that 5 days post infection, only neurointermediate pituitary lobectomy (NIL) reduces the number of intestinally recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser confocal microscopy, we observed that the mean intensity of all tested Th1 cytokines was markedly diminished, even in the duodenum of infected controls. In contrast, a high level of expression of these cytokines was noted in the NIL infected hamsters. Likewise, a significant decrease in the fluorescence intensity of Th2 cytokines (with the exception of IL-4) was apparent in the duodenum of control and sham infected hamsters, compared to animals with NIL surgeries, which showed an increase in the expression of IL-5 and IL-13. Histology of duodenal mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located along the lamina propria, which was related to the presence of the parasite. We conclude that hormones from each pituitary lobe affect the gastrointestinal immune responses to T. spiralis through various mechanisms.

Partial Text

In addition to the hypothalamic control of adenohypophysial and neurohypophysial hormones (neuroendocrine system), which regulate body growth, cell differentiation, maturation, metabolism, reproduction, stress, aging, lactation, and hydro electrolytic balance, a great deal of information indicates that in the maintenance of body homeostasis, pituitary hormones interact with the immune system, as well as during bacterial, parasitic, viral, and auto-antigenic challenges [1]–[7] to overcome infectious and inflammatory diseases. The mediators in the immunoneuroendocrine interactions, include cytokines from immune and inflammatory cells, receptors, hormones, neuropeptides and neurotransmitters. Communication between the immune and neuroendocrine system begins when cytokines released during inflammation interact with cytokine receptors in peripheral nerves, or when cytokines from the inflammatory loci are blood-borne to the several nerve nuclei in the central nervous system (CNS), where they interact with cytokine receptors. After neural integration (mainly in the hypothalamus), the autonomous nervous system and the hypophysiotropic hormones regulate pituitary hormone secretion, which together with local cytokines integrate an adequate immune response. Thus, after the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis through glucocorticoids (cortisol and corticosterone), HPA axis has a modulator/suppressor effect on the immune system preventing an excessive immune response [8], [9]. The HPA axis is also involved in the adaptation and maintenance of homeostasis during critical illness, and during bacterial, parasitic, viral, and autoimmune/inflammatory diseases [10]–[13]. Growth hormone (GH), prolactin (PRL), and the neurohypophysial arginine vasopressin (AVP) are immunomodulators/immunostimulators [4], [14]–[21], whereas sex hormones of the hypothalamic-pituitary-gonadal (HPG) axis affect the susceptibility of the immune system when facing immune challenges, thus determining the development of infections and autoimmune diseases [22].

The host-parasite relationship implies biochemical co-evolution and cross-talk between both the physiological and metabolic systems [42], [48]. The purpose of this work was to examine the effects of HYPOX, AL, and NIL on the cytokine expression pattern during the immune response against the intestinal infection by T. spiralis. Our findings demonstrate that pituitary hormones differentially influence the cytokine expression in spleen and intestine during the intestinal infection by T. spiralis. Removal of the pituitary gland (HYPOX) affects the activity of phagocytes, the main cells of the innate immunity involved in killing T. spiralis[49], [50]. It has been previously demonstrated that peritoneal macrophages from HYPOX rats show an impaired TNFα response to the in vitro stimulation with lipopolysaccharide [30], being also less effective in killing Salmonella serovar typhimurium than those cells derived from rats having intact pituitaries [26]. Interestingly, GH injections are able to enhance the resistance of both intact and HYPOX rats following a challenge with Salmonella serovar typhimurium[27], [30]. This enhanced resistance correlates with an increased capacity in peritoneal macrophages from those animals to generate reactive oxygen species (ROS), such as superoxide anion and hydrogen peroxide [27]. Additionally, GH is also capable to activate human monocytes for an enhanced intermediate ROS production in vitro[51], [52]. We have also reported that HYPOX and NIL, causes increasing bacterial colonization of Peyer patches and spleen, accompanied by a decrease in the intestinal secretory profile of IgA, as well as low IgM and IgG serum levels during the intestinal infection with Salmonella serovar typhimurium[1], [3]. All together this information supports the view that both GH and neurohypophysial hormones might play a role as stimulators/modulators of the immune system in peripheral and gut-associated lymphoid tissue (GALT). However, so far there is no information concerning any parasite infection regarding the role of pituitary hormones on both the systemic and intestinal immune regulation. Thus, this is the first set of experiments attempting to demonstrate the role of pituitary hormones in the control of T. spiralis or any other helminth.