Disodium cromoglycate treatment reduces TH2 immune response and immunohistopathological features in a murine model of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an emergent chronic disease of the esophagus. The immunopathological process in EoE is characterized by Th2 immune response and prominent eosinophilic influx, in response to common food allergens. The classical treatment consists of allergen elimination diet and systemic/topical corticosteroid therapy. Nevertheless, patients do not always comply to treatment, and the prolonged corticosteroid therapy can cause side effects, therefore, there is an immediate need for new therapeutic approach for EoE. Disodium cromoglicate (DSCG) is a substance broadly used in allergic asthma treatment, and a well-known mast cell activation stabilizer. However, its effect in EoE have not been evaluated yet. This study aimed to assess the effects of DSCG treatment in an EoE experimental model. Male Balb/C mice were subcutaneously sensitized for five days with OVA, and subsequently orally OVA-challenged, DSCG administration was performed between the OVA-challenges. DSCG treatment not only reduced eosinophilic and mast cell influx, as well as reduced fibrosis. In addition, tslp, GATA3, IL-5, FoxP3 and IL-10 mRNA expression were reduced in esophageal mucosa, associated with lower Th2 (CD3+CD4+GATA3+IL4+) and B cells (CD19+CD40+) number in peripheral lymphoid organs. In conclusion, the data demonstrate DSCG treatment was effective in reducing mast cell activation and Th2 immune response, important immunopathological EoE features. Therefore, the use of DSCG as an EoE treatment can be considered a promising therapeutic approach to treat this disease.

Arginine and manganese supplementation on the immune competence of broilers immune stimulated with vaccine against Salmonella Enteritidis.

This experiment was conducted to evaluate the combined effects of manganese-amino acid complex and arginine supplementation on the immune competence of broilers. On the day of hatch 640 male Cobb 500 broiler chicks assigned to two study groups (immune stimulate and non-stimulated). A 2 × 2 factorial arrangement of treatments was used with two manganese sources (MnSO4 or manganese-amino acid complex - MnAA) and two digestible Arg:Lys ratios (1.12 or 1.20). The treatments are: IM (80 ppm MnSO4); MnAA (40 ppm MnSO4 + 40 ppm MnAA); IM+Arg: 80 ppm MnSO4+ L-Arg (Arg:DigLys 1.20); MnAA+Arg: 40 ppm MnSO4 + 40 ppm MnAA + L-Arg (Arg:Lys 1.20). For treatments 1 and 2, the digestible Arg:Lys ratio was 1.12, considered normal for corn-soybean meal-based diets. Birds in the immune stimulated group received a dose of Salmonella Enteritidis vaccine. For growth performance and lymphoid organ development, no significant results were observed. Non-stimulated birds fed diets with Arg supplementation had higher percentage of mucosal T helper, T helper and T cytotoxic, compared to the normal Arg:Lys ratio (1.12). In the immune stimulated birds, broilers fed exclusive IM diet had a higher amount of T helper, T cytotoxic, activated T cytotoxic, and APC cells compared to broilers fed MnAA. The inorganic Mn diets, resulted in higher humoral antibody level (increased IgM levels) only when associated with supplementation of L-Arg. However, the use of an associated Mn source, could support high levels of IgM in commercial levels of Arg. No differences were observed to macrophage phagocytic activity analyses.

Chronic Consumption of Sweeteners and Its Effect on Glycaemia, Cytokines, Hormones, and Lymphocytes of GALT in CD1 Mice.

BACKGROUND: The consumption of sweeteners has increased in recent years, being used to control body weight and blood glucose. However, they can cause increased appetite, modification of immune function, and secretion of hormones in the GALT. OBJECTIVE: To assess the effect of chronic sweetener consumption on glycaemia, cytokines, hormones, and GALT lymphocytes in CD1 mice. MATERIAL AND METHODS: 72 CD1 mice divided into 3 groups were used: (a) baseline, (b) middle, and (c) final. Groups (b) and (c) were divided into 4 subgroups: (i) Control, (ii) Sucrose, (iii) Sucralose, and (iv) Stevia. The following were determined: body weight, hormones (GIP, insulin, and leptin), lymphocytes CD3+T cells and CD19+B cells, IgA+ plasma cells, and cytokines (IL-4, IL-5, IFN-γ, and TNF-α). RESULTS: Sucralose reduces secretion of GIP and glycaemia but does not modify insulin concentration, increases body weight, and reduces food intake. Stevia increases the secretion of GIP, insulin, leptin, body weight, and glycaemia but keeps food consumption normal. Sucralose and Stevia showed a higher percentage of CD3+T cells, CD19+B cells, and IgA+ plasma cells in Peyer's patches, but only Stevia in lamina propria. CONCLUSION: Sweeteners modulate the hormonal response of cytokines and the proliferation of lymphocytes in the intestinal mucosa.

Macrophage activity and histopathology of the lymphohematopoietic organs in male Wistar rats orally exposed to single or mixed pesticides.

The noxious effects of low or effective dose exposure to single or mixed pesticides on macrophage activity and the lymphohematopoietic organs were investigated. Male Wistar rats were orally exposed to dichlorvos, dicofol, endosulfan, dieldrin and permethrin, either as single or combined mixtures during a 28-day study containing eight groups: one group received a semipurified diet (non-treated); two groups received a semipurified diet containing low dose mixture (dieldrin 0.025 mg/kg, endosulfan, 0.6 mg/kg, dicofol 0.22 mg/kg, dichlorvos 0.23 mg/kg, permethrin 5 mg/kg) or an effective dose mixture (dichlorvos 2.3 mg/kg, dicofol 2.5 mg/kg, endosulfan 2.9 mg/kg, dieldrin 0.05 mg/kg and permethrin 25.0 mg/kg), respectively; the other five groups received a semipurified diet containing each single pesticide in effective doses. At sacrifice, the thymus, spleen, mesenteric lymph nodes, Payer's patches and bone marrow were removed for histological analysis. Peritoneal macrophages were obtained to determine the phagocytosis and spreading indexes and tumoral necrosis factor alpha (TNF-α), nitric oxide (NO) and H2O2 production. Exposure to pesticide mixtures did not alter the percentage of macrophage phagocytosis and spreading, TNF-α production or the NO and H2O2 release when compared to the non-treated group. Neither was there any apparent evidence that a pesticide mixture at low or effective doses altered the histological structure of the lymphohematopoietic organs. The findings indicate that short-term treatment with pesticide mixtures did not induce an apparent immunotoxic effect in male Wistar rats.

Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

Spontaneous and experimental intoxication of cattle by Simarouba versicolor A. St.-Hill (Simaroubaceae).

This study describes an outbreak of Simarouba versicolor intoxication in cattle from Mato Grosso do Sul, Brazil, and reproduces it experimentally. Clinical signs of the affected animals were weakness, tremors, hind limbs incoordination, reluctance to move, sternal and lateral recumbency and death. The main necropsy findings, observed in the abomasum and in segments of the small and large intestines, were diffuse redness and mucosal and serosal swelling. Histological examination revealed necrosis of lymphoid tissues and necrotizing enterocolitis. One experiment was carried out using 3 male calves to test the toxicity of a single dose of S. versicolor leaves at 15 g/kg, 5 g/kg and 2.5 g/kg. Clinical signs, necropsy findings and histological examination of calves receiving 15 g/kg and 5 g/kg leaves were similar to those of cattle from the intoxication outbreak. The calf fed 2.5 g/kg leaves developed clinical symptoms of poisoning and recovered naturally. In a second experiment, two male calves received daily administration of S. versicolor leaves at 1.5 g/kg and 2.5 g/kg for 10 days. They developed clinical signs of intoxication within 24 h and recovered eight to nine days after the leaves were administered. These findings suggest that S. versicolor was responsible for the outbreak studied, although this plant does not have cumulative intoxication effects on cattle.

HIV-induced T-cell activation/exhaustion in rectal mucosa is controlled only partially by antiretroviral treatment.

Peripheral blood T-cells from untreated HIV-1-infected patients exhibit reduced immune responses, usually associated with a hyperactivated/exhausted phenotype compared to HAART treated patients. However, it is not clear whether HAART ameliorates this altered phenotype of T-cells in the gastrointestinal-associated lymphoid tissue (GALT), the main site for viral replication. Here, we compared T-cells from peripheral blood and GALT of two groups of chronically HIV-1-infected patients: untreated patients with active viral replication, and patients on suppressive HAART. We characterized the T-cell phenotype by measuring PD-1, CTLA-4, HLA-DR, CD25, Foxp3 and granzyme A expression by flow cytometry; mRNA expression of T-bet, GATA-3, ROR-γt and Foxp3, and was also evaluated in peripheral blood mononuclear cells and rectal lymphoid cells. In HIV-1+ patients, the frequency of PD-1(+) and CTLA-4(+) T-cells (both CD4+ and CD8+ T cells) was higher in the GALT than in the blood. The expression of PD-1 by T-cells from GALT was higher in HIV-1-infected subjects with active viral replication compared to controls. Moreover, the expression per cell of PD-1 and CTLA-4 in CD4(+) T-cells from blood and GALT was positively correlated with viral load. HAART treatment decreased the expression of CTLA-4 in CD8(+) T cells from blood and GALT to levels similar as those observed in controls. Frequency of Granzyme A(+) CD8(+) T-cells in both tissues was low in the untreated group, compared to controls and HAART-treated patients. Finally, a switch towards Treg polarization was found in untreated patients, in both tissues. Together, these findings suggest that chronic HIV-1 infection results in an activated/exhausted T-cell phenotype, despite T-cell polarization towards a regulatory profile; these alterations are more pronounced in the GALT compared to peripheral blood, and are only partiality modulated by HAART.

Immune cells recruitment and activation by Tityus serrulatus scorpion venom.

Despite several studies showed that the Tityus serrulatus scorpion venom (Tsv) induces an inflammatory response, just a few have investigated the effect of the venom on the immune response. Therefore, the aim of this study was to evaluate alterations of venom application on lymphoid organs and on the recruitment and activation of cells and also on the cytokine production. Swiss male mice (2-3 months, 20-25 g) received a non-lethal dose of crude Tsv (200 µg/kg), diluted in sterile PBS by subcutaneous route. Control animals received only sterile PBS. The animals were sacrificed after 30, 120 and 360 min. The inflammatory parameters studied were skin histology at the site of venom application, leukocyte count, and blood cytokine levels (IL-6, IL-10, and TNF-α). Inguinal lymph node, spleen and bone marrow cellularity was determined for evaluation of the Tsv effect on immune system organs. The results showed that Tsv caused no local inflammation, but it induced an increase of blood neutrophils and serum IL-6, TNF-α and IL-10. After 360 min of envenomation there was a reduction in the cells number from peritoneum and spleen, but there was an increase in the cell number from lymph nodes. In conclusion, the Tsv induces systemic alterations characterized by changes in the cell number in lymphoid organs, increase pro and anti-inflammatory cytokines.

Haematological and immunological effects of repeated dose exposure of rats to integerrimine N-oxide from Senecio brasiliensis.

This study is the first in the literature to focus attention on the possible immunotoxic effect of integerrimine N-oxide content in the butanolic residue (BR) of Senecio brasiliensis, a poisonous hepatotoxic plant that contains pyrrolizidine alkaloids (PAs). PAs have been reported as a pasture and food contaminant and as herbal medicine used worldwide and are responsible for poisoning events in livestock and human beings. After the plant extraction, BR extracted from Senecio brasiliensis was found to contain approximately 70% integerrimine N-oxide by elemental and spectral analyses ((1)H and (13)C NMR), which was administered to adult male Wistar Hannover rats at doses of 3, 6 and 9 mg/kg for 28 days. Body weight gain, food consumption, lymphoid organs, neutrophil analysis, humoural immune response, cellular immune response and lymphocyte analysis were evaluated. Our study showed that integerrimine N-oxide could promote an impairment in the body weight gain, interference with blood cell counts and a reducing T cell proliferative activity in rats; however, no differences in the neutrophil activities, lymphocytes phenotyping and humoural and cellular immune responses were observed. It is concluded that doses of integerrimine N-oxide here employed did not produce marked immunotoxic effects.

Effects of gestational and lactational fenvalerate exposure on immune and reproductive systems of male rats.

The aim of this study was to determine the consequent reproductive developmental and immunotoxic effects due to exposure to fenvalerate during pregnancy and lactation in male offspring of maternal-treated rats. Pregnant rats were treated daily by oral gavage with 40 or 80 mg/kg of fenvalerate or corn oil (vehicle, control), from d 12 of pregnancy to d 21 of lactation. Immune and reproductive developmental effects were assessed in male offspring at postnatal days (PND) 40 (peripuberty), 60 (postpuberty), and 90 (sexual maturity). Treatment with the higher dose (80 mg/kg) resulted in convulsive behavior, hyperexcitability, and mortality in 45% of the dams. Fenvalerate was detected in the fetus due to placental transfer, as well as in pups due to breast-milk ingestion, persisting in male offspring until PND 40 even though pesticide treatment was terminated on PND 20. However, fenvalerate did not produce marked alterations in age of testicular descent to the scrotum and prepucial separation, parameters indicative of puberty initiation. In contrast, at puberty, there was a reduction in testicular weight and sperm production in male offspring of maternal-treated rats. At adulthood, the sperm counts and fertility did not differ between control and treated groups. Testosterone levels were not changed at any time during reproductive development. Similarly, no apparent exposure-related effects were detected in the histological structures of the lymphohematopoietic system. Data indicate that fenvalerate, in this experimental model, interfered with initial development of the male reproductive system, but that these effects on sperm production or fertility did not persist into adulthood. There was no apparent evidence that fenvalerate altered testosterone levels or produced a disruption in male endocrine functions.

Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration.

Chitosan is a cationic polysaccharide derived from the partial deacetylation of chitin, which exhibits particular properties: interacts with negatively charged sites on the cell surface; changes the permeability of intestinal epithelium, enhancing the uptake of peptides and proteins; and activates leukocytes. Antigens coadministered or encapsulated with the polysaccharide show improved mucosal and systemic humoral immune responses, although the mechanism is poorly understood. Herein, we characterized in Peyer's patches mesenteric lymph nodes and spleen molecular events triggered after oral administration of chitosan in the absence of protein antigen. Sixteen hours after feeding, we studied the uptake and distribution of the polysaccharide, the phenotype of recruited antigen-presenting cells (APC), the induction of cytokines such as tumor necrosis factor alpha, interleukin (IL)-12, IL-4, IL-10, and transforming growth factor-beta (TGF-beta), and the activation of T lymphocytes. We show here that the uptake of chitosan at inductive mucosal sites involves CD11b/c+ APC and that chitosan feeding increases the percentage of OX62+ dendritic cells, which up-regulate the major histocompatibility complex class II antigens without changing the expression of costimulatory CD80 or CD86 molecules. The polysaccharide elicits the release of IL-10 as well as the expression of IL-4 and TGF-beta in mucosa, and in spleen, the activation of CD3+ T cells occurs. Our results demonstrate that chitosan acts by enhancing the T helper cell type 2 (Th2)/Th3 microenvironment in the mucosa. A single dose of this polysaccharide exhibits local and systemic effects, and its activity could be relevant in the maintenance of the intestinal homeostasis.

Chemically induced immunotoxicity in a medium-term multiorgan bioassay for carcinogenesis with Wistar rats.

A variety of chemicals can adversely affect the immune system and influence tumor development. The modifying potential of chemical carcinogens on the lymphoid organs and cytokine production of rats submitted to a medium-term initiation-promotion bioassay for carcinogenesis was investigated. Male Wistar rats were sequentially initiated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4hydroxybutyl)nitrosamine (BBN), dihydroxy-di-n-propylnitrosamine (DHPN), and 1,2-dimethylhydrazine (DMH) during 4 weeks. Two initiated groups received phenobarbital (PB) or 2-acetylaminofluorene (2-AAF) for 25 weeks and two noninitiated groups received only PB or 2-AAF. A nontreated group was used as control. Lymphohematopoietic organs, liver, kidneys, lung, intestines, and Zymbal's gland were removed for histological analysis. Interleukin (IL)-2, IL-12, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), IL-10, and transforming growth factor beta1 (TGF-beta1) levels were determined by ELISA in spleen cell culture supernatants. At the fourth week, exposure to the initiating carcinogens resulted in cell depletion of the thymus, spleen and bone marrow, and impairment of IL-2, IL-12, and IFN-gamma production. However, at the 30th week, no important alterations were observed both in lymphoid organs and cytokine production in the different groups. The results indicate that the initiating carcinogens used in the present protocol exert toxic effects on the lymphoid organs and affect the production of cytokines at the initiation step of carcinogenesis. This early and reversible depression of the immune surveillance may contribute to the survival of initiated cells facilitating the development of future neoplasia.

Effect of dietary fat on lymphocyte proliferation and metabolism.

The effect of diets enriched with fat containing different fatty acids on glucose and glutamine metabolism of mesenteric lymph nodes lymphocytes, spleen, and thymus and lymphocyte proliferation was examined. The following fat-rich diets were tested: (1) standard chow (CC); (2) medium chain saturated fatty acids (MS)--coconut fat oil; (3) long chain saturated fatty acids (LS)--cocoa butter; (4) monounsaturated fatty acids (MU)--canola oil (n-9); (5) polyunsaturated fatty acids (PU)--soybean oil (n-6). Of the fat-rich diets tested, MS was the one to present the least pronounced effect. Lymphocyte proliferation was reduced by LS (64 per cent), MU (55 per cent), and PU (60 per cent). Hexokinase activity was enhanced in lymph node lymphocytes by PU (67 per cent), in the spleen by MS (42 per cent), and in the thymus by PU (30 per cent). This enzyme activity was reduced in the spleen (33 per cent) by LS and MU (35 per cent). In the thymus, this enzyme activity was reduced by LS (26 per cent) and MU (13 per cent). Maximal phosphate-dependent glutaminase activity was raised in lymphocytes by MS (70 per cent) and MU (20 per cent). This enzyme activity, however, was decreased in lymphocytes by PU (26 per cent), in the spleen by LS (15 per cent), and in the thymus by MU (44 per cent). Citrate synthase activity was increased in lymphocytes by MU (35 per cent), in the spleen by LS (56 per cent) and MU (68 per cent), and in the thymus by LS (42 per cent). This enzyme activity was decreased in lymphocytes by PU (24 per cent) only. [U-14C]-Glucose decarboxylation was raised by all fat-rich diets; MS (88 per cent). LS (39 per cent), MU (33 per cent), and PU (50 per cent), whereas [U-14C]-glutamine decarboxylation was increased by LS (53 per cent) and MU (55 per cent) and decreased by MS (17 per cent). The results presented indicate that the reduction in lymphocyte proliferation due to LS, LU and PU could well be a consequence of changes in glucose and glutamine metabolism.

Effect of the administration of fish oil by gavage on activities of antioxidant enzymes of rat lymphoid organs.

1. The effect of administration of fish oil by gavage on catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities of the lymphoid organs and liver was compared with those of soybean oil and cocoa butter. 2. Fish oil did not affect the activities of SOD and CAT but reduced that of GSH-Px in the spleen. In contrast, cocoa butter reduced the CAT activity in the thymus and liver, and soybean oil decreased CAT activity in the thymus. 3. The content of thiobarbituric acid reactive substances of the lymphoid organs was not modified but was increased in plasma.

Effect of RN-301 immunomodulator on bronchus-associated lymphoid tissue (BALT) in protein depleted rats at weaning.

It has been previously demonstrated in Wistar rats that severe protein deprivation at weaning, even after refeeding with a 20% casein diet for 21 days, provokes alterations in IgA+ B cell and T cell populations from gut and GALT (gut associated lymphoid tissue) that are reverted by immunomodulator IM-104. In the present report, we investigate the influence of RN-301 (quite similar to IM-104) given by the oral or subcutaneous route during the protein deprivation period, in the seeding of BALT with IgA+ B and CD5+ T cells. The immunomodulator RN-301 contains LPS from E. coli and membrane and ribosomal fractions of P. acne. Tissue sections of the lower respiratory tract were studied by immunohistochemistry. The immunomodulator RN-301 administered by the oral route favours the significant increase in the seeding of the BALT lamina propria with IgA+ B and CD5+ T cells (p < 0.001). However, the RN-301 given by the subcutaneous route does not favour the repopulation of the BALT lamina propria. The ribosomal fractions from P. acne associated with LPS from E. coli contained in the immunomodulator RN-301 administered by the oral route may rescue the small resting lymphocytes in the gut-associated lymphoid tissue (GALT). This event favours their proliferation and migration to the BALT.

Effect of RN-301 immunomodulator on bronchus-associated lymphoid tissue (Balt) in protein depleted rats at weaning

It has been previously demonstrated in Wistar rats that severe protein deprivation at weaning, even after refeeding with a 20 percent casein diet for 21 days, provokes alterations in IgA+ B cell and T cell populations from gut and GALT (gut associated lymphoid tissue) that are reverted by immunomodulator IM-104. In the present report, we investigated the influence of RN-301 (quite similar to IM-104) given by the oral or subcutaneous route during the protein deprivation period, in the seeding of BALT with IgA+ B and CD5+T cells. The immunomodulator RN-301 contains LPS from E. coli and membrane and ribosomal fractions of P. acne. Tissue sections of the lower respiratory tract were studied by immunohistochemistry. The immunomodulator RN-301 administered by the oral route favours the significant increase in the seeding of the BALT lamina propria with IGA+B and CD5+T cells (p < 0.001). However, the RN-301 given by the subcutaneous route does not favour the repopulation of the BALT lamina propria. The ribosomal fractions from P. acne associated with LPS from E. coli contained in the immunomodulator RN-301 administered by the oral route may rescue the small resting lymphocytes in the gut-associated lymphoid tissue (GALT). This event favours their proliferation and migration to the BALT.

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

Effect of RN-301 immunomodulator on bronchus-associated lymphoid tissue (Balt) in protein depleted rats at weaning

It has been previously demonstrated in Wistar rats that severe protein deprivation at weaning, even after refeeding with a 20 percent casein diet for 21 days, provokes alterations in IgA+ B cell and T cell populations from gut and GALT (gut associated lymphoid tissue) that are reverted by immunomodulator IM-104. In the present report, we investigated the influence of RN-301 (quite similar to IM-104) given by the oral or subcutaneous route during the protein deprivation period, in the seeding of BALT with IgA+ B and CD5+T cells. The immunomodulator RN-301 contains LPS from E. coli and membrane and ribosomal fractions of P. acne. Tissue sections of the lower respiratory tract were studied by immunohistochemistry. The immunomodulator RN-301 administered by the oral route favours the significant increase in the seeding of the BALT lamina propria with IGA+B and CD5+T cells (p < 0.001). However, the RN-301 given by the subcutaneous route does not favour the repopulation of the BALT lamina propria. The ribosomal fractions from P. acne associated with LPS from E. coli contained in the immunomodulator RN-301 administered by the oral route may rescue the small resting lymphocytes in the gut-associated lymphoid tissue (GALT). This event favours their proliferation and migration to the BALT. (AU)

Imunossupressäo experimental em camundongos: aspectos histopatológicos dos órgäos linfóides após tratamento com dexametasona e inoculaçäo de Candida albicans / Experimental imunossupressin in mice: histologycal aspects of the linfoid tissue after administration of dexamethasone and inoculation with Candida albicans

Foi realizada imunossupressäo experimental com corticosteróides em camundongos usando 1 mg/kg/dia de exametsona durante uma semana. Para verificar os efeitos imunossupressores da droga, sobre os tecidos linfóides, inoculamos 1 ml de 1.10 de Candida albicans, por via endovenosa, após o tratamento. Observamos a instalaçäo e evoluçäo da infecçäo durante doze dias e analisamos os aspectos histológicos do baço, timo, linfonodos, rins, fígado, pulmöes e pele, que foram retirados, em intervalos regulares, de animais tratados somente com dexametasona e somente com Candida albicans, ou com ambos os dois tratamentos. Os resultados obtidos nos levaram a concluir que ocorre imunossupressäo com essa dosagem de dexametasona e que o baço foi o órgäo mais atingido. A candidíase isoladamente também provocou imunossupressäo, afetando principalmente o timo. Os efeitos imunossupressores dos dois tratamentos se somaram quando houve a associaçäo dos mesmos