-The post-weaning period in pigs is characterized by an immediate but transient drop in feed intake resulting in severe undernutrition and growth check. This in turn affects various aspects of small intestinal architecture and function leading to gut-associated disorders and often diarrhea. Among these, villus atrophy and digestive enzyme activity depression have been documented. More recent investigations clearly demonstrate early signs of local inflammation including immune cell infiltration and increased pro-inflammatory cytokine gene expression, signs of cytoprotection through up-regulation of so-called heat shock proteins, indications of tissue alterations by proteases (stromelysin) and finally epithelial functional disorders in mineral absorption/secretion and permeability. This is followed by a regenerative phase, probably stimulated by feed intake resumption, resulting in down-regulation of many intestinal indicators. However, some of them then display new spatio-temporal adult-type adaptive patterns of maturation. A limited number of substances, particularly nitrogenous compounds and complex preparations of animal origin (colostrum, plasma) have proven to be successful, at least partly, in minimizing post-weaning intestinal disturbances. Thus further research in intestinal physiology, in association with microbiology and immunology, is warranted to strengthen our understanding of the mechanisms of gut disorders in order to provide a better rational basis for designing suitable alternatives to in-feed antibiotics for pigs. clairement montré des signes précoces d'inflammation incluant une infiltration cellulaire et l'expression accrue des gènes de plusieurs cytokines inflammatoires, une cytoprotection renforcée par la sur-expression des protéines du choc thermique, des indications d'altérations tissulaires par des protéases (stromélysines), et finalement des désordres fonctionnels épithéliaux d'absorption et de sécrétion minérales et de la perméabilité intestinale. Ceci est suivi par une phase de régénération intestinale, probablement stimulée par la reprise de consommation alimentaire, et conduisant à un retour à la normale de plusieurs indicateurs. Cependant, certains d'entre eux ont évolué vers des profils spatio-temporels adaptatifs de type adulte. Un nombre limité de substances, particulièrement des composés azotés et des produits animaux (colostrum, plasma) ont démontré leur capacité, au moins partielle, à minimiser les perturbations digestives post-sevrage. De nouvelles recherches en physiologie digestive, en association avec la microbiologie et l'immunologie, sont nécessaires pour renforcer notre compréhension des mécanismes des troubles digestifs. Ceci permettra de fournir des bases plus rationnelles pour développer des solutions alternatives satisfaisantes aux antibiotiques dans les aliments pour porcelets.intestin / nutrition / physiopathologie / porcelet / sevrage

Cytokines play a central role in immune cell response, but they also participate in the maintenance of tissue integrity. Changes in the cytokine network of the pig gut may be expected at weaning, because abrupt changes in dietary and environmental factors lead to important morphological and functional adaptations in the gut. This study measured the gene expression of 6 inflammatory cytokines along the small intestine (SI) and the proximal colon in 28-d-old piglets (n = 45) at different time points (0, 1, 2, 5 and 8 d) postweaning, using RT-PCR. Villus-crypt architecture and enzymatic activities of lactase and sucrase in the SI were also examined. The results confirmed that weaning is associated with morphological and enzymatic changes in the SI. In addition, the data indicated that cytokine response in the gut could be divided into two periods: an early acute response (0 to 2 d postweaning) and a late long-lasting response (2 to 8 d postweaning). Between d 0 and d 2, the levels of IL-1beta, IL-6, and TNF-alpha messenger RNA (mRNA) increased. Marked upregulation of IL-1beta mRNA occurred in most parts of the intestine, whereas IL-6 and TNF-alpha mRNA markedly increased only at specific sites in the intestine. Between d 2 and d 8, the levels of IL-1beta, IL-6, and TNF-alpha mRNA rapidly returned to preweaning values, except that the level of TNF-alpha mRNA remained high in the distal SI. Levels of IL-12 subunit p40 (IL-12p40) and IL-18 mRNA also decreased, compared to those on d 0. Taken together, these results demonstrate that weaning in piglets is associated with an early and transient response in gene expression of inflammatory cytokines in the gut.

Fifteen 8-week-old conventional pigs were selected from a farm where pigs were suffering from postweaning multisystemic wasting syndrome (PMWS). Ten of the animals were diseased pigs showing typical signs of PMWS (wasting and respiratory disorders) and positive for infection with porcine circovirus type 2 (PCV2), and the other five animals selected as controls were pen-mate, apparently healthy pigs. Blood samples and lymphoid tissues were taken from each animal for haematological, serological and histopathological studies. Also, cytokine mRNA expression of IL-1beta, IL-2, IL-4, IL-8, IL-10, IL-12p40 and IFN-gamma from inguinal and bronchial lymph nodes, tonsils, spleen and thymus was determined by semi-quantitative RT-PCR. Pigs suffering from PMWS showed severe alterations of haematological parameters such as anaemia, lymphopenia with decrease of CD8(+) and IgM(+) cells, monocytosis and neutrophilia. Also, extensive lymphocyte depletion and altered cytokine mRNA expression patterns were seen in most of the examined lymphoid organs. Those cytokine mRNA alterations were characterized by an overexpression of IL-10 mRNA in thymus and IFN-gamma mRNA in tonsils, and by decreases in the mRNA expression of several cytokines as IL-2 and IL-12p40 in the spleen, IL-4 in tonsils, and IFN-gamma, IL-10, IL-12p40 and IL-4 in inguinal lymph nodes. Also, the IL-10 mRNA overexpression was histologically associated with the thymic depletion and atrophy observed in PMWS pigs. In conclusion, the cytokine mRNA imbalance, specially the increased mRNA levels of IL-10 in the thymus, jointly with the histopathological and haematological disorders, are highly indicative of a T-cell immunosuppression, enhancing the notion that the immune system of PMWS-affected pigs is severely impaired.

-European-wide directives are in place to establish a sustainable production of pigs without using production enhancers and chemotherapeutics. Thus, an economically-viable pig production is now only possible when the physiological mechanisms of defense against pathogens and tolerance against nutrients and commensal bacteria in the intestinal immune system are taken into account. During the postnatal period the piglet is facing first the time large amounts of new antigens and at weaning a second wave of nutritional antigens is entering the intestinal tract. The appropriate development of humoral and cellular functions of the intestinal immune system is essential for optimum growth and performance of the piglets. The integrity of the intestinal surfaces is a prerequisite of intestinal immunity and tolerance. Secretory IgA serves to exclude harmful antigens from uptake. The induction of intestinal immune reactions starts with antigen presentation by professional antigen presenting cells of Peyer's patches and mesenteric lymph nodes. In addition, the intestinal lamina propria serves as a mucosal compartment for regulation of immune responses. Here especially T regulatory cells (CD4 + CD25 + ) have their function for maintaining intestinal homeostasis. The network of mucosal T and B cells develops after birth in a programmed sequence; it is almost completed at week 7 after birth. Weaning is associated with changes in the regulation of the lymphoid cells in the mucosa. In small and large intestine increases in pro-and anti-inflammatory cytokines were observed after weaning in lymphocytes. Epithelial cells were studied both in intestinal samples and in vitro. Here the cytokine patterns provide evidence that weaning is inducing a transient inflammation of the mucosa. Piglets weaned under conventional conditions have a thicker mucosa than pigs weaned from isolators. Cells of isolator-reared pigs show slightly higher levels of activation markers -probably * Corresponding author: hermann-josef.rothkoetter@medizin.uni-magdeburg.de 326 C.R. Stokes et al.reflecting the interaction of the foreign protein derived from bovine milk. The results presented in this overview demonstrate that further effort is necessary to elucidate the function of the porcine intestinal immune system in the postnatal period and at the time of weaning to provide criteria for porcine intestinal health.inflammation / intestinal immunity / mucosa / nutrition / pig / postnatal / weaning Résumé -Développement postnatal de l'immunité intestinale chez le porcelet : implications pour le processus de sevrage. Des directives européennes ont été adoptées, en vue de mettre en place une production durable de porcs sans facteurs de croissance ni antibiotiques. Dans ce contexte, un élevage porcin ne sera économiquement viable que si sont pris en compte les mécanismes physiologiques de défense contre les agents pathogènes, et de tolérance vis-à-vis des aliments et des bactéries commensales, mécanismes engageant le système immunitaire intestinal des animaux. ...

Previous studies have shown that gamma interferon (IFN-␥) plays a major role in natural resistance to Salmonella typhimurium during the early phase of infection. To assess whether the level of natural resistance in mice is related to the level of IFN-␥ gene expression, we compared IFN-␥ mRNA levels by means of reverse transcriptase-PCR in the spleens of genetically susceptible Ity s (C57BL/6 and BALB/c) and resistant Ity r (CBA and DBA/2) mice during the first 5 days of infection. The mRNA expression of interleukin-10 (IL-10), a cytokine which antagonizes IFN-␥ effects, was also investigated. Mice were infected with 10 3 CFU of the virulent strain S. typhimurium C5, a dose which is lethal within a week for susceptible mice only. IFN-␥ mRNA increased to similar levels in both susceptible and resistant mice, suggesting that susceptibility to S. typhimurium infection is not related to defective IFN-␥ gene expression. In contrast, IL-10 mRNA reached much higher levels in susceptible than in resistant mice. Similar results were found in Ity congenic mice, confirming a link between the presence of the Ity s allele and a high level of IL-10 gene expression during infection. High levels of IL-10 mRNA in susceptible mice correlated with high IL-10 serum levels (on day 5), whereas IL-10 was not detectable in the sera of resistant mice. However, administration of neutralizing anti-IL-10 monoclonal antibodies did not modify the course of infection. To evaluate the influence of bacterial multiplication on IL-10 mRNA expression, susceptible mice were infected with an attenuated strain of S. typhimurium. This strain induced a low level of IL-10 mRNA expression. When susceptible mice were immunized with an attenuated strain and challenged with the virulent strain, they inhibited the growth of the challenge bacteria and exhibited a low level of IL-10 mRNA. In contrast, when resistant mice were infected with a high (lethal) dose of the virulent strain, they exhibited a high level of IL-10 mRNA. Taken together, these results indicate that the level of IL-10 gene expression correlates with the level of bacterial multiplication in the organs and that the high level of IL-10 mRNA in Ity s mice is a consequence rather than the cause of their susceptibility to S. typhimurium infection. Salmonella typhimurium is a facultative intracellular bacterium which can enter and multiply within macrophages and also nonphagocytic cells (18). During experimental infection in mice, the bacteria replicate mainly in the spleen and liver and induce a disease similar to human typhoid fever. Following intravenous challenge, acquired immunity to mouse salmonellosis is mainly T cell mediated, with the participation of both CD4 ϩ and CD8 ϩ subpopulations (21, 28). The antibody response also contributes to acquired immunity (11, 20). The survival of animals before the development of specific acquired immunity depends on natural resistance. Natural resistance to S. typhimurium infection in mice is regulated by several genes (30), in particular Ity, which contr...