Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system.

The immune system is under strong circadian control, and circadian desynchrony is a risk factor for metabolic disorders, inflammatory responses and cancer. Signaling pathways that maintain circadian rhythms (CRs) in immune function in vivo, and the mechanisms by which circadian desynchrony impairs immune function, remain to be fully identified. These experiments tested the hypothesis that the hypothalamic circadian pacemaker in the suprachiasmatic nucleus (SCN) drives CRs in the immune system, using a non-invasive model of SCN circadian arrhythmia. Robust CRs in blood leukocyte trafficking, with a peak during the early light phase (ZT4) and nadir in the early dark phase (ZT18), were absent in arrhythmic hamsters, as were CRs in spleen clock gene (per1, bmal1) expression, indicating that a functional pacemaker in the SCN is required for the generation of CRs in leukocyte trafficking and for driving peripheral clocks in secondary lymphoid organs. Pinealectomy was without effect on CRs in leukocyte trafficking, but abolished CRs in spleen clock gene expression, indicating that nocturnal melatonin secretion is necessary for communicating circadian time information to the spleen. CRs in trafficking of antigen presenting cells (CD11c(+) dendritic cells) in the skin were abolished, and antigen-specific delayed-type hypersensitivity skin inflammatory responses were markedly impaired in arrhythmic hamsters. The SCN drives robust CRs in leukocyte trafficking and lymphoid clock gene expression; the latter of which is not expressed in the absence of melatonin. Robust entrainment of the circadian pacemaker provides a signal critical to diurnal rhythms in immunosurveilliance and optimal memory T-cell dependent immune responses.

Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pig

Effects of yeast selenium supplementation on the growth performance, meat quality, immunity, and antioxidant capacity of goose.

The aim was to investigate the effects of yeast selenium (YS) supplementation on the growth performance, meat quality, immunity, and antioxidant variables of geese. A total of 96 one-day-old geese with similar body weight were randomly divided into four groups, with three replicates per group and eight geese in each replicate. The birds were fed basal diets supplemented with 0, 0.10, 0.30, 0.50 mg/kg YS (on selenium basis) during the 63-day experiment. Yeast selenium supplementation showed no effect on the growth performance of geese, but significantly improved the meat quality. No changes in ash or fat content were observed in breast muscle, but significant (p < 0.05) protein content increase was detected in the 0.1 and 0.5 mg/kg groups. Yeast selenium supplementation significantly (p < 0.05 or p < 0.01) promoted Se deposition in liver, kidney, pancreas, and muscle and the highest increases were all detected in the 0.5 mg/kg group. Yeast selenium supplementation enhanced the organ and cellular immunity of geese, but did not alter the humoral immunity. Furthermore, dietary YS significantly (p < 0.05) promoted the antioxidant capacity of both muscle and liver, but the effects varied with YS levels and organs. Hence, dietary YS supplementation was a good measure to improve the meat quality, Se content, immunity function, and antioxidant capacity of goose.

Inulin and probiotics in newly weaned piglets: effects on intestinal morphology, mRNA expression levels of inflammatory marker genes and haematology.

The study aimed at determining the effect of inulin and/or a multispecies probiotic formulation on gastrointestinal tract (GIT) morphology, immunological and haematological parameters. Forty-eight newly weaned piglets were assigned to four feeding groups, receiving a standard basal diet (control), supplemented with 0.4% inulin, probiotics (1 x 10(9) CFU/kg as fed, enterococci, lactobacilli, bifidobacteria) or a combination of both (synbiotic). After four weeks of ad libitum feeding piglets were slaughtered and intestinal tissue samples were obtained for histometry. Additional tissue samples of the GIT, mesenteric lymph nodes, blood, liver and spleen were taken for mRNA expression analysis of cell turnover (CDK4, caspase3, IGF I), transcription factor NFkappaB and inflammatory marker genes (TNFalpha, TGFbeta). Changes in histometry occurred predominantly in the small intestine, showing higher jejunal villi when probiotics were administered alone (p < 0.10). Inulin decreased the number of acidic goblet cells in jejunal villi (p < 0.05), whereas probiotics increased neutral goblet cells in ileal villi (p < 0.05). Though inflammatory marker genes were uninfluenced by treatment in the proximal GIT, the colon showed downregulations induced by inulin (TNFalpha: p < 0.10, TGFbeta: p < 0.05). Gene expression of CDK4 was upregulated in the jejunum and of TGFbeta in the mesenteric lymph nodes in the probiotic groups. Interestingly, the probiotic group alone exhibited upregulations in cell turnover marker genes in the colon and blood. Furthermore, for numerous parameters, inulin and probiotics led to no synergistic but antagonistic interactions.

Influence of adding fish oil to parenteral nutrition on gut-associated lymphoid tissue.

BACKGROUND: Lack of enteral nutrition reduces gut-associated lymphoid tissue (GALT) mass and function, a mechanism underlying the increased morbidity of infectious complications in severely injured or critically ill patients. Strategies to restore parenteral nutrition (PN)-induced changes of GALT mass and function have been pursued. However, the influences of adding fish oil to PN on gut immunity remain to be clarified. METHODS: Male Institute of Cancer Research (ICR) mice (n = 50) were randomized to 4 groups: ad libitum chow (chow), fat free PN (fat (-)-PN), PN + fish oil (FO-PN), and PN + safflower oil (SO-PN). The PN groups were given isocaloric and isonitrogenous PN solutions. The FO- and SO-PN groups received 20% of total calories from fat emulsions. After 5 days of feeding, lymphocytes from Peyer's patches (PPs), the intraepithelial space (IE), and the lamina propria (LP) of the entire small intestine were isolated. GALT lymphocyte numbers and phenotypes (CD4+, CD8+, alphabetaTCR+, gammadeltaTCR+, B220+ cells) were determined. Immunoglobulin A (IgA) levels of small intestinal washings were also measured by enzyme-linked immunosorbent assay. Another set of mice (n = 24) was used to determine plasma fatty acid compositions after feeding. RESULTS: Lymphocyte numbers from PPs and the LP and intestinal IgA levels were significantly lower in the PN groups than in the chow group, with no significant differences between any 2 PN groups. The FO- and SO-PN groups showed moderate recovery of IE cell numbers compared with the fat (-)-PN group. Omega-3 and omega-6 fatty acid levels were increased with fish and safflower oil additions, respectively, compared with the fat (-)-PN group. CONCLUSIONS: Adding fish oil to PN does not exacerbate PN-induced GALT changes but rather partially reverses these changes, with increased plasma omega-3 fatty acid levels.

Hyperbaric oxygen and lymphoid system function: a review supporting possible intervention in tissue transplantation.

This review addresses the many ways that hyperbaric oxygen (HBO2) has been found to mitigate immune reactions, many of which are involved in rejection of allograft transplants, and thus offers a rationale for its possible use as an adjunct to help preserve and protect transplanted tissues. Rejection may involve both immunological reactions of the lymphoid system, or lymphoid-independent damage from trauma or other factors, including reperfusion injury. Lymphoid-induced damage involves cellular elements such as CD4 and macrophage cell types, as well as both proinflammatory and inhibitory cytokines. Cytokines such as TNFs and interleukins activate T-cells and macrophages, resulting in endothelial damage and its consequences. The immunosuppressive effects of HBO2 include suppression of autoimmune symptoms, decreased production of IL-1 and CD4 cells, and increased percentage and absolute number of CD8 cells. HBO2 normalizes cell-bound immunity and decreases the serum concentration of immune complexes. Studies have shown MHC class I expression to be altered when cultures were exposed to HBO2, so as to become undetectable by monoclonal antibodies or cytotoxic T lymphocytes. HBO2 has been used in support of replanted rabbit ear grafts, spinal cord tissue transplants, dislocated young permanent teeth in children, replanting of fingers, free fibula reconstruction of segmental mandibular resections, autogenous free bone grafts, transplantations of the cornea, and liver transplants. In addition to its specific effects on the immune system, HBO2 improves tissue oxygenation, reduces free radical damage during reperfusion, maintains marginally ischemic tissue, and accelerates wound healing. These properties make HBO2 a promising intervention to be tested in transplantation recipients.

A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1.

Secondary lymphoid organs (spleen, lymph nodes and Peyer's patches) are divided into compartments, such as B-cell zones (follicles) and T-cell zones, which provide specialized environments for specific steps of the immune response. Migration of lymphocyte subsets into these compartments is essential for normal immune function, yet the molecular cues guiding this cellular traffic are poorly defined. Chemokines constitute a family of chemotactic cytokines that have been shown to direct the migration of leukocytes during inflammation and which may be involved in the constitutive homing of lymphocytes into follicles and T-cell zones. Here we describe a novel chemokine, B-lymphocyte chemoattractant (BLC), that is strongly expressed in the follicles of Peyer's patches, the spleen and lymph nodes. BLC strongly attracts B lymphocytes while promoting migration of only small numbers of T cells and macrophages, and therefore is the first chemokine to be identified that is selective towards B cells. An orphan chemokine receptor, Burkitt's lymphoma receptor 1 (BLR-1), has been found to be required for B-cell migration into lymphoid follicles. We show that BLC stimulates calcium influx into, and chemotaxis of, cells transfected with BLR-1. Our results indicate that BLC functions as a BLR-1 ligand and may guide B lymphocytes to follicles in secondary lymphoid organs.

Alteraçöes metabólicas e funcionais em células e órgäos do sistema imunológico de ratos induzidas pela administraçäo intragástrica do óleo de peixe / Metabolic and functional changes in cells and organs of immune system of rats due to the fish oil administrated by gavage

O consumo de cápsulas de óleo de peixe (OP) por humanos visa a atenuaçäo dos sintomas e prevençäo de várias patologias. As alteraçöes metabólicas e funcionais em células e órgäos do sistema imunológico causadas pelo OP pela administraçäo intragástrica (AIG) foram avaliadas. Ratos recém-desmamados (50-70 g) foram submetidos a AIG diária com óleo de peixe, óleo de soja ou manteiga de cacau (0,4 por cento do peso), por 28 dias. Os dados da AIG do OP foram também comparados com os da dieta enriquecida com OP. Foram avaliados: aumento de permeabilidade vascular (reaçäo anafilática), funcionalidade de macrófagos (produçäo de 'H IND. 2O IND. 2', 'O IND. 2' e fagocitose), proliferaçäo de linfócitos, a atividade máxima das enzimas: hexoquinase, glicose-6-fosfato desidrogenase, citrato sintase (metabolismo de glicose), catalase, glutationa peroxidase e superóxido dismutase (antioxidantes) no baço, linfonodo mesentérico e timo. A concentraçäo de TBARs nos mesmos órgäos e no plasma e a capacidade antioxidante do plasma foram também determinadas

A scanning electron microscopy and computer image processing morphometric study of the pharmacological regulation of patency of the peritoneal stomata.

The experiment on mice was carried out by injecting intraperitoneally Chinese materia medica for treating hepatocirrhosis with ascites. Observations and a quantitative analysis were carried out on the pharmacological regulation of the peritoneal stomata by using a scanning electron microscope (SEM) and a computer image processing system attached to the SEM. There was a significant increase in both the diameter (P < 0.05) and distribution density (P < 0.01) of the peritoneal stomata in the red sage root and alismatis rhizome groups, whereas the effect of poria and poria peel was not significant compared with the control group (P > 0.05). Our findings confirm the effect of red sage root and alismatis rhizome on the regulation of the peritoneal stomata, which can enhance the absorption of ascitic fluid, taking into consideration the absorbent function of these stomata. They indicate that the patency of peritoneal stomata can vary in response to the effect of some Chinese materia. They also suggest that the ascites is drained mainly by means of enhancing the patency of the stomata and lymphatic absorption of the stomata during the process of treatment by traditional Chinese medicine.

[Morphofunctional restructuring of the nervous system of the lymphoid organs during electrostimulation of the hypothalamus]. / Morfofunktsional'naia perestroika nervnogo apparata limfoidnykh organov pri élektrostimuliatsii gipotalamusa.

The intramural nervous apparatus of rabbit lymphoid organs was examined after 15 and 30 sessions of electric stimulation of the posterior hypothalamus. The function of nerve cells was evaluated by cytophotometry according to the content of catecholamines and acetylcholinesterase (ACE) activity. In the mesenteric lymph nodes, stimulation led to a decrease in the activity of both adrenergic and ACE-containing nerve cells. The spleen demonstrated a reduction in the catecholamine content in the perivascular nerve plexuses, with a simultaneous rise of the catecholamine content in the fibers located in the parenchyma, which evidences inhibition of the neurogenous mechanisms of vasomotor control and possible selective activation of the sympathetic mechanisms involved in the regulation of the immunogenesis. Thymic preparations impregnated with silver salts manifested high argyrophilia of the nerve cells, characteristic of the reactive phase of the destructive process. The problems of the hypothalamic effects on the blood supply and functions of the immune system organs are discussed.