The Central Nervous (CNS) and Immune Systems (IS) are the two major adaptive systems which respond rapidly to numerous challenges that are able to compromise health. The defensive response strictly linking innate to acquired immunity, works continuously to limit pathogen invasion and damage. The efficiency of the innate response is crucial for survival and for an optimum priming of acquired immunity. During infection, the immune response is modulated by an integrated neuro-immune network which potentiates innate immunity, controls potential harmful effects and also addresses metabolic and nutritional modifications supporting immune function. In the last decade much knowledge has been gained on the molecular signals that orchestrate this integrated adaptive response, with focus on the systemic mediators which have a crucial role in driving and controlling an efficient protective response. These mediators are also able to signal alterations and control pathway dysfunctions which may be involved in the persistence and/or overexpression of inflammation that may lead to tissue damage and to a negative metabolic impact, causing retarded growth. This review aims to describe some important signalling pathways which drive bidirectional communication between the Immune and Nervous Systems during infection. Particular emphasis is placed on pro-inflammatory cytokines, immunomodulator hormones such as Glucocorticoids (GCs), Growth hormone (GH), Insulin-like Growth Factor-1 (IGF-1), and Leptin, as well as nutritional factors such as Zinc (Zn). Finally, the review includes up-to-date information on this neuroimmune cross-talk in domestic animals. Data in domestic animal species are still limited, but there are several exciting areas of research, like the potential interaction pathways between mediators (i.e. cytokine-HPA regulation, IL-6-GCS-Zn, cytokines-GH/IGF-1, IL-6-GH-Leptin and thymus activity) that are or could be promising topics of future research in veterinary medicine.

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The aim of this study was to investigate the direct effect of leptin on GH gene expression and secretion and the role of nitric oxide as a possible mediator in pig anterior pituitary cells. Pituitary cells from adult sows were treated for 4 or 24 h with rhleptin (from 0.1 nM to 1 microM) alone or in association with GHRH (10 nM) or hexarelin (10 nM). At the end of incubation, medium was collected for GH and nitric oxide determination by ELISA and Griess test, respectively. Total RNA was collected from cells, and GH gene expression was measured by RT-PCR. Leptin significantly (P < 0.001) stimulated GH secretion in both incubation periods. The maximum response was induced by 10 nM leptin; furthermore, a significant interaction (P < 0.002) between leptin and GHRH (P < 0.03) and between leptin and hexarelin was observed when the molecules were used in association. GH gene expression was significantly increased (at least P < 0.05) by hexarelin, GHRH, and leptin (1000 and 100 nM) after 24 h of treatment. Leptin (10 nM and 1 microM) significantly (P < 0.05) increased nitric oxide production, whereas S-nitroso-N-acetyl-penicillamine (from 0.01-1000 nM) significantly (P < 0.05) stimulated GH secretion. These data demonstrate that leptin directly influences GH regulation at the pituitary level, and nitric oxide may be involved in this function.

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The effects of dietary nucleotide supplementation from 9 days of age until the end of post-weaning on piglets hormonal and immune responses and on growth performance were investigated. During lactation (days 9 to 21) and post-weaning (days 22 to 55) 10 [HBI Fomeva11 3 (Large White 3 Landrace)] litters (n 5 108 piglets) had ad libitum access to two standard diets, both supplemented with 0% (T0 group) or 0.1% (T1 group) of yeast extract nucleotides. BW of piglets at days 21 (P , 0.10), 35 and 55 (P , 0.05) was greater in T1 compared with T0. Feed intake was not different between groups (P . 0.05). Cortisol content was lower in T1 than in T0 at days 28 and 35 (P , 0.05), whereas growth hormone was lower at day 35 (P , 0.05). Levels of IGF-1 were similar across groups (P . 0.05). Nucleotide-supplemented diets increased lymphocyte subpopulation CD42CD81 high at days 21 and 35 (P , 0.05), whereas CD41CD82 cells were higher in T1 than in T0 at day 21 (P , 0.05). Peripheral blood mononuclear cells cytokine expression was influenced by dietary nucleotide supplementation. At weaning, interleukin (IL)-6 and IL-1b expression was lower (P , 0.05) in T1 compared with T0, whereas the expression of interferon (IFN)-g and IL-10 was higher (P , 0.05). At day 28, piglets in T1 showed higher values of tumor necrosis factor (TNF)-a expression than T0 and lower values of IL-10 expression (P , 0.05). Dietary nucleotide supplementation had a suppressive effect on IL-6 and IL-10 expression (P , 0.05) at day 35. On the contrary, the expression of IFN-g, TNF-a and IL-1b was enhanced (P , 0.05). In conclusion, these results suggest that starting a dietary nucleotide supplementation before weaning can improve the adaptive capabilities of weaned piglets to the stressors, enhancing the growth performance.

The aim of this study was to examine the effect of recombinant human leptin on growth hormone (GH) secretion in perifused anterior pituitary slices from adult pigs. Anterior pituitary slices from sows were perifused and treated with recombinant human leptin (10 nM) and GH-releasing hormone (GHRH; 1 nM). In some experiments, pituitary slices were coincubated with stalk median eminence (SME). In a subset of the coincubation experiments, immunoneutralization of endogenous GHRH and somatostatin (SRIH) release was performed with antisera to GHRH and SRIH. Leptin increased GH secretion in pituitary slices alone (up to 100% vs. control at 40 min) as well as in pituitary slices coincubated with SME (up to 122% vs. control at 40 min). A significant difference was observed in GH secretion from pituitary slices when the tissue was coincubated with leptin and GHRH at a low concentration (0.1 nM), but not when GHRH was used at 1 and 10 nM. Furthermore, anti-SRIH antiserum increased GH release from pituitary slices in coincubation experiments with SME. Finally, SRIH secretion was significantly reduced by leptin (down by 35% vs. control from 0 to 30 min of treatment) in cultured SME. These data show that leptin is effective in stimulating GH secretion by acting at two different levels: (1) it stimulates GH secretion directly from pituitary slices, and (2) it reduces SRIH tone from the median eminence and, indirectly, increases GH secretion from the pituitary. These results support the hypothesis that leptin may be an interesting hormonal mediator of growth and related metabolic effects by acting directly on the hypothalamic-pituitary axis.

BackgroundThis study was aimed at evaluating the clinical protection, the level of Porcine circovirus type 2 (PCV2) viremia and the immune response (antibodies and IFN-γ secreting cells (SC)) in piglets derived from PCV2 vaccinated sows and themselves vaccinated against PCV2 at different age, namely at 4, 6 and 8 weeks. The cohort study has been carried out over three subsequent production cycles (replicates). At the start/enrolment, 46 gilts were considered at first mating, bled and vaccinated. At the first, second and third farrowing, dams were bled and re-vaccinated at the subsequent mating after weaning piglets. Overall 400 piglets at each farrowing (first, second and third) were randomly allocated in three different groups (100 piglets/group) based on the timing of vaccination (4, 6 or 8 weeks of age). A fourth group was kept non-vaccinated (controls). Piglets were vaccinated intramuscularly with one dose (2 mL) of a commercial PCV2a-based subunit vaccine (Porcilis® PCV). Twenty animals per group were bled at weaning and from vaccination to slaughter every 4 weeks for the detection of PCV2 viremia, humoral and cell-mediated immune responses. Clinical signs and individual treatments (morbidity), mortality, and body weight of all piglets were recorded.ResultsAll vaccination schemes (4, 6 and 8 weeks of age) were able to induce an antibody response and IFN-γ SC. The highest clinical and virological protection sustained by immune reactivity was observed in pigs vaccinated at 6 weeks of age. Overall, repeated PCV2 vaccination in sows at mating and the subsequent higher levels of maternally derived antibodies did not significantly interfere with the induction of both humoral and cell-mediated immunity in their piglets after vaccination.ConclusionsThe combination of vaccination in sows at mating and in piglets at 6 weeks of age was more effective for controlling PCV2 natural infection, than other vaccination schemas, thus sustaining that some interference of MDA with the induction of an efficient immune response could be considered. In conclusion, optimal vaccination strategy needs to balance the levels of passive immunity, the management practices and timing of infection.