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Biomedical subjects

E Isolauri

Publications and source records attributed to E Isolauri.

At least 109 records · Page 6Linked to original sources

Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis.

We compared different lactic acid bacteria for their effect on the immune response to rotavirus in children with acute rotavirus gastroenteritis. After initial oral rehydration, 49 children aged 6 to 35 months with rotavirus gastroenteritis randomly received either Lactobacillus casei subsp. casei strain GG (LGG), L. casei subsp. rhamnosus (Lactophilus), or a combination of Streptococcus thermophilus and L. delbrückii subsp. bulgaricus (Yalacta) twice daily for 5 days. Serum antibodies to rotavirus, total number of immunoglobulin-secreting cells (ISC), and specific antibody-secreting cells (sASC) to rotavirus were measured at the acute stage and at convalescence. The mean (SD) duration of diarrhea was 1.8 (0.8) days in children who received LGG, 2.8 (1.2) days in those receiving Lactophilus, and 2.6 (1.4) days in those receiving Yalacta (F = 3.3, p = 0.04). The ISC response was comparable in the three study groups, but the rotavirus-specific immune responses were different. LGG therapy was associated with an enhancement of IgA sASC to rotavirus and serum IgA antibody level at convalescent stage. We conclude that certain strains of lactic acid bacteria, particularly LGG, promote serum and intestinal immune responses to rotavirus, and thus may be important in establishing immunity against rotavirus reinfections.

Acute Disease↗

Viable versus inactivated lactobacillus strain GG in acute rotavirus diarrhoea.

The effect of viable or heat inactivated human Lactobacillus casei strain GG on rotavirus immune responses in patients with rotavirus diarrhoea was assessed. Rotavirus serum IgA enzyme immunoassay antibody responses were higher in infants treated with viable L casei strain GG than in those treated with inactivated L casei strain GG. There was a significant difference at convalescence with rotavirus specific IgA secreting cells found in 10/12 infants receiving viable but only 2/13 infants receiving inactivated L casei strain GG. The results indicate that viable L casei strain GG stimulate rotavirus specific IgA antibody responses, theoretically significant in the prevention of reinfections.

Acute Disease↗

Gut flora in normal and disordered states.

Infections of the gastrointestinal tract are a major health problem for both adults and children worldwide. Changes in the normal human gut microflora result in the development of intestinal disorders. Pathogenic bacteria alter the intestinal microecology and intestinal colonization resistance. A healthy gastrointestinal microflora forms a barrier against invading organisms. Normal intestinal microbes and some probiotic bacteria can enhance the host's defence mechanisms against pathogens. They can also improve intestinal immunity by adhering to intestinal mucosa and stimulating local immune responses. Thus the maintenance of a balanced intestinal microecology improves the ability to preserve intestinal integrity.

Antibiosis↗

The treatment of cow's milk allergy.

Current approach to the treatment of food allergy is directed towards elimination diets. The treatment of choice of cow's milk allergy is complete avoidance of cow's milk antigens. In infants it is necessary to use substitute formulas. The completeness of the elimination diet is questionable since immunoreactive components of cow's milk protein can be detected in substitute formulas and even breast milk. In most cases, extensively hydrolyzed cow's milk-derived formulas can be safely introduced, and these are efficient and clinically and metabolically well tolerated. The approach to control allergic inflammation by antigen elimination, however, is not satisfactory, particularly in patients with multiple food allergies. New approaches are urgently needed for teh treatment of cow's milk allergy. These may include antigen elimination supplemented with synthetic amino acid-derived formulas, immunotherapy to counteract the immunologic dysfunction and stabilization of the gut mucosal barrier to strengthen endogenous defence mechanisms.

Humans↗

Oral bacteriotherapy for viral gastroenteritis.

The effect of orally administered lactobacilli on acute rotavirus diarrhea was tested in 42 well-nourished children ages 5-28 months. After oral rehydration, the patients were randomized to a study group, receiving human Lactobacillus casei strain GG 10(10) colony-forming units twice daily for five days, or a control group not given lactobacilli. Lactobacillus GG was found in the feces in 83% of the study group. The diarrheal phase was shortened in that group. Dietary supplementation with lactobacilli significantly influenced the bacterial enzyme profile: urease activity during diarrhea transiently increased in the control group but not in the study group; F = 8.6, P = 0.01. No intergroup differences were found in beta-glucuronidase, beta-glucosidase, and glycocholic acid hydrolase levels. We suggest that rotavirus infection gives rise to biphasic diarrhea, the first phase being an osmotic diarrhea and the second associated with overgrowth of specifically urease-producing bacteria. Oral bacteriotherapy appears a promising means to counteract the disturbed microbial balance.

Administration, Oral↗

Lymphocyte response to cow's milk proteins in patients with cow's milk allergy: relationship to antigen exposure.

The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2-4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and/or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.

Administration, Oral↗

Evidence for eosinophil activation in cow's milk allergy.

To assist in identifying pathogenetic mechanisms in different clinical manifestations of cow's milk allergy (CMA), the involvement of eosinophil cells in immunoinflammatory reactions was evaluated. The study population comprised 28 patients, aged from 5.8 to 43.0 months, who had challenge-proven CMA, manifested either cutaneously (n = 17) or gastrointestinally (n = 11). A clinical cow's milk challenge was performed in hospital after a 4 week cow's milk elimination period. Eosinophil activation in vivo was studied by measuring the serum level of eosinophil cationic protein (ECP) before the oral cow's milk challenge, mean (SD) 27 (12) hours after commencing the challenge and one week later. These results were compared to those of 80 non-allergic age-matched controls. During the challenge, the level of ECP increased from 6.2 (4.5, 8.0) micrograms/L to 20.0 (9.5, 30, 4) micrograms/L in CMA patients with skin manifestations but not in those with gastrointestinal symptoms. The increase was shown to be transient. We conclude that eosinophil degranulation is an important immunologic mechanism leading to allergic inflammation in cutaneously manifested CMA.

Blood Proteins↗

A prospective study of humoral immune responses to cow milk antigens in the first year of life.

Previous studies have shown that in cow milk allergy the specific immune response to dietary cow milk antigens is deficient. This study aimed at delineating the development of humoral immune response to cow milk antigens in healthy infants. Twenty-five healthy newborns were enrolled, and seen at scheduled visits at the ages of three, six and eleven months, and they formed two groups: those breastfed and those fed adapted cow milk formulae. The local immune response in the gut was approximated using the ELISPOT assay of circulating antibody secreting cells. At the age of three months, in the formula fed group, cells secreting specific IgA to cow milk antigens were detected despite low levels of IgA serum antibodies. The total number of IgA secreting cells increased with age (p = 0.001). The milk in the infant diet directly influenced this development so that the age related increase was significantly greater in the formula fed group (p = 0.04). The results indicate that diet has a significant effect on the developing immune system, and that healthy infants are able to respond in an antigen specific fashion to dietary antigens, which may be central in attaining clinical tolerance of such antigens.

Animals↗

New concepts of allergy to cow's milk.

CMA is a diagnostic and therapeutic problem in the field of pediatrics. The response to oral cow's milk challenge was evaluated in patients with suspective CMA. To investigate immune mechanisms in different subtypes of CMA, suppressor activity, in vitro IFN-gamma and IL-4 generation, eosinophil activation and humoral immune response were measured. Also, changes in the function of the immune system were evaluated when patients had clinically recovered from CMA. The results of different measurements were correlated with the patients' clinical response to cow's milk challenge. The prechallenge suppressor activity was found to be low in patients with challenge-proven CMA when compared with those clinically negative to oral cow's milk challenge but had normalized after a 4-18 month milk-elimination period in patients who had recovered from CMA. IFN-gamma generation was low in patients with active CMA but had clearly enhanced in patients recovering from CMA. The serum concentration of ECP increased significantly during oral cow's milk challenge in patients with cutaneously manifested CMA. Measured by the ELISPOT method, the patients with active CMA mounted a high, non-antigen-specific immune response but were unable to direct the antigen-specific response, especially in the IgA class. After a follow-up of a mean 13.5 months on cow's milk elimination diet, the immune response to cow's milk antigens had developed in patients who had recovered from CMA. The development in the capacity to mount an adequate immune response to specific protein antigens, especially in the IgA class, can be interpreted as deriving from the development in T-lymphocyte regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats.

BACKGROUND: Lactobacilli constitute a major part of the microflora throughout the gastrointestinal tract. This study aimed to investigate the effect of lactobacilli on the gut mucosal barrier. METHODS: Rat pups were divided into three experimental feeding groups at the age of 14 days. In addition to normal maternal milk, group "milk" received a daily gavage of cow milk, group "milk-GG" received Lactobacillus casei strain GG with cow milk, and controls were gavaged with the same volume of water. At 21 days, the absorption of horseradish peroxidase across patch-free jejunal segments and segments containing Peyer's patches was studied in Ussing chambers. RESULTS: The mean absorption of intact horseradish peroxidase expressed in ng.h-1.cm-2, was significantly different in the study groups in both patch-free segments (controls, 9 [95% confidence interval, 7-12]; milk, 72 [60-87]; and milk-GG, 15 [4-52]) and in segments containing Peyer's patches (controls, 3 [1-17]; milk, 80 [43-151]; and milk-GG, 15 [4-56]). There was a significant increase in the frequency of cells secreting antibodies to beta-lactoglobulin (enzyme-linked immunospot assay) in the milk-GG group. CONCLUSIONS: Prolonged cow milk challenge in suckling rats increases gut permeability to intact proteins, whereas Lactobacillus GG counteracts this permeability disorder. The results suggest a link between the intensity of the antigen-specific immune response and stabilization of the mucosal barrier.

Animals↗

Increased in vitro intestinal permeability in suckling rats exposed to cow milk during lactation.

Specific mucosal barrier functions of the gut develop in the newborn to combat the constant challenge of foreign antigens. To determine whether exposure to cow milk antigens interferes with this maturational process, jejunal permeability to macromolecules and the activation of immune mechanisms were studied in preweaning rats. At the age of 14 days, rat pups were divided into three feeding groups. Controls (n = 18) remained on normal maternal milk; group CM (n = 27) additionally received a daily gavage feed of cow milk; and in group D (n = 23), cow milk was given to dams. At 21 days, when "gut closure" normally occurs, intestinal in vitro absorption of horseradish peroxidase in its intact form was significantly higher in group CM and in group D than in controls (F = 5.6; p = 0.006): group CM: mean, 37.8 ng/h/cm2; 95% confidence interval (CI), 19.4-73.6; group D: mean, 26.9 ng/h/cm2; 95% CI, 8.2-88.2; controls: mean, 4.0 ng/h/cm2; 95% CI, 1.2-13.9. In association with increased jejunal permeability, there was enhanced jejunal eosinophilic infiltration in group CM. In group D, the number of specific antibody-secreting cells in peripheral blood against beta-lactoglobulin was significantly higher than in group CM and controls. These data indicate that there is a critical period in development when feeding cow milk antigens delays gut closure. They further suggest that mucosal barrier function is impaired due to a local hypersensitivity reaction to cow milk antigens, irrespective of the protection of maternal milk or maternal antigen processing.

Age Factors↗

Immunologic disturbances in cow's milk allergy, 1: Delayed maturation of suppressor activity.

To assist in identifying pathogenetic mechanisms in different subtypes of cow's milk allergy (CMA), the function of immunoregulatory T-lymphocytes was studied. The study population consisted of 23 patients, mean [95% confidence interval] age of 25.6 [19.5, 33.6] months, who had challenge-proven cow's milk allergy manifested with either skin (n = 9) or gastrointestinal (n = 14) symptoms; in addition, 13 age-matched disease controls were studied. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The suppressor activity of isolated lymphocytes was measured in vitro by a cell coculture at rechallenge and in 10/23 patients at diagnosis. At diagnosis, patients with CMA (n = 10) showed a decreased mean [95% CI] suppressor activity, induced by either Concanavalin A, 7[-2,15]%, or cow's milk, 3[-8,14]% as compared with disease controls (n = 13), 19[15,24]% and 24[17,31]%; F = 7.1, p = 0.004 and F = 6.7, p = 0.005, respectively. At rechallenge the suppressor activity, induced both by Concanavalin A and cow's milk, reached the level of disease controls only in patients who had acquired clinical tolerance to cow's milk (n = 13/23), but not in those retaining CMA (n = 10/23). Our results indicate that the maturation of suppressor function is delayed in CMA, which might be of primary importance in the etiopathogenesis of CMA.

Child, Preschool↗

Immunologic disturbances in cow's milk allergy, 2: Evidence for defective interferon-gamma generation.

We have investigated the role of interferon-gamma (IFN-gamma) in the regulation of antigen-specific T-cell function in patients with cow's milk allergy. The study population consisted of 22 patients, aged from 7.6 to 56.9 months, who had challenge-proven cow's milk allergy (CMA) manifested with either skin (n = 9) or gastrointestinal (n = 13) symptoms. In addition, 11 age-matched children and 6 adults, mean (SD) age 31 (7) years, were studied as controls. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The spontaneous and mitogen-induced IFN-gamma and interleukin-4 (IL-4) generation of isolated lymphocytes was evaluated in vitro with commercial ELISA Kits at diagnosis and at reassessment. At diagnosis, the IFN-gamma production was not detectable in patients with CMA as compared with control children. IL-4 production was almost undetectable in all subjects in this study. However, at reassessment the CMA patients who had acquired clinical tolerance to cow's milk (n = 16) showed enhanced IFN-gamma production, when compared with that of control children, but still lower when compared with that of healthy adults. Our results indicate that the maturation of IFN-gamma producing T-cells is delayed in CMA, which could lead to a disturbance in the regulation of T-cell function. This defect might be an important etiologic factor for CMA.

Child, Preschool↗

Diet during rotavirus enteritis affects jejunal permeability to macromolecules in suckling rats.

We studied the influence of diet during diarrhea on gut mucosal barrier in a suckling rat model. Rat pups were inoculated with IDIR virus (a group B rotavirus) at 10 d of age. Beginning 2 d postinfection, in addition to maternal milk, group CM received a daily gavage of cow milk and group GG received Lactobacillus casei strain GG, a human strain previously shown to survive the passage through the gastrointestinal tract and temporarily colonize the gut. Group CMGG received a combination of these, and control animals were gavaged with tap water. At 21 d of age, jejunal absorption of intact and degraded horseradish peroxidase (HRP) in Ussing chamber was markedly higher in IDIR virus-infected than in noninfected controls. In the two groups gavaged with cow milk, group CM and group CMGG, the numbers of specific antibody-secreting cells (enumerated by the solid-phase enzyme-linked immunospot assay) against beta-lactoglobulin were significantly higher than in the groups that had not received cow milk. In parallel with immune system activation, a statistically significant increase in the absorption of intact HRP (mean and 95% confidence interval, ng x h-1 x cm-2) was detected: group CM, 302 (155, 586); group CMGG, 174 (56, 545); infected controls, 121 (57, 257); and group GG, 44 (8, 254). A decrease in the uptake of intact HRP (F = 3.64, p = 0.06) and degraded HRP (F = 9.50, p = 0.004) was associated with the introduction of L. casei GG to the diet, irrespective of coexposure to cow milk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Local immune response in patients with cow milk allergy: follow-up of patients retaining allergy or becoming tolerant.

To assist in identifying factors that determine the clinical outcome of cow milk allergy, we subjected to rechallenge 37 patients with a history of cow milk allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1 months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells among peripheral blood lymphocytes primed during provocation by milk antigens, giving indirect evidence of local immune response in the gut. Patients with persistent cow milk allergy (n = 13) had milder reactions at rechallenge than they had shown at the time of diagnosis. Numbers of immunoglobulin-secreting cells in these patients increased significantly from a geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to 2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445 (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of immunoglobulin-secreting cells did not increase during provocation. The total number of IgA-secreting cells before rechallenge was significantly higher than it had been before the initial challenge. The patients who acquired cow milk tolerance also had specific antibody-secreting cells of IgA isotype before the second challenge. These results indicate that in cow milk allergy the ability to mount a local immune response against cow milk antigens, particularly in the IgA class, is related to the suppression of clinical sensitivity.

Animals↗

Preponderance of IgM from blood lymphocytes in response to infantile rotavirus gastroenteritis.

Immune responses triggered by acute rotavirus infection in infants are poorly defined. To obtain indirect evidence as to gut immune response to rotavirus, the solid phase enzyme linked immunoassay (ELISPOT) of immunoglobulin and specific antibody secreting cells among circulating blood lymphocytes was used. Seventeen well nourished patients from seven to 25 months of age were studied during the peak of rotavirus infection, and in convalescence. A transient but distinct immunoglobulin secreting cell response in IgM and IgG, but not in IgA, classes was found during the diarrhoeal phase. This response included a quantitatively prominent activation of specific antibody secreting cells against rotavirus in the IgM class, mean (95% confidence interval (CI)) 82 (32, 210)/10(6) cells v 8 (4, 17)/10(6) cells in convalescence, p = 0.01. The response in the IgA class was not significant. The results indicate that local immune mechanisms are activated in rotavirus diarrhoea. They further suggest that although IgA is the predominant immunoglobulin operative in the gastrointestinal tract, this may not be the case in infantile rotavirus enteritis.

Antibody Specificity↗

Cow's milk provocation induces an immune response to unrelated dietary antigens.

The activation of immune mechanisms was evaluated by the solid phase enzyme linked immunoassay of immunoglobulin and specific antibody secreting cells in 27 patients (aged from nine to 69 months), subjected to a diagnostic cow's milk challenge or a rechallenge. A significant rise in the total number of immunoglobulin secreting cells was associated with clinically positive (n = 17), but not a negative (n = 10) cow's milk challenge in all immunoglobulin isotypes. The number of specific antibody secreting cells against beta lactoglobulin, mean (95% confidence interval), increased from 4.8 (1.4, 15.8) to 16.9 (5.5, 52.7) specific antibody secreting cells/10(6) cells, p = 0.02, and against casein from 2.2 (0.8, 6.1) to 7.5 (2.5, 22.5) specific antibody secreting cells/10(6) cells, p = 0.01, in patients positive to challenge in the IgM class only, indicating defective immune elimination of milk antigens. In addition to the specific immune response to cow's milk antigens, an increase in IgM specific antibody secreting cells against an unrelated dietary antigen, gliadin, from 8.2 (2.1, 31.1) to 31.0 (14.2, 67.6) specific antibody secreting cells/10(6) cells, p = 0.01, was observed. These results indicate that cow's milk challenge, in patients who have cow's milk allergy, induces a strong non-antigen specific immune response that includes a response against unrelated antigens concomitantly present in the intestinal lumen. Activation of such immune mechanisms may hence reflect increased antigenic load caused by the immune mediated lesion in the gut mucosa.

Antibody Specificity↗