lactoferrin and Gastritis

Lactoferrin possesses antibiotic, antiinflammatory, and immune-modulating properties that may be active against the gastritis-, ulcer- and cancer-inducing bacterium Helicobacter pylori. In vitro testing of bovine and human lactoferrin by several laboratories has shown significant bacteriostatic and bactericidal activity. Subsequent in vivo testing of bovine lactoferrin in animal models of H. pylori infection has shown beneficial effects of this agent. Our laboratory has utilized a mouse model that is infected with the feline strain of this bacterium, H. felis. The resulting gastritis that develops in this model and the effects of bovine lactoferrin and recombinant human lactoferrin (from Aspergillus niger var. awamori, Agennix Inc., Houston, Tex.) treatment were assessed by various measures. Infected animals treated with orally administered lactoferrin showed reversals in all parameters. In addition, when recombinant human lactoferrin was used in combination with low doses of amoxicillin or tetracycline, there was an enhancement in gastritis-reducing activity. Possible mechanisms for these effects of lactoferrin are discussed. Lactoferrin has significant, orally active in vivo actions and should be further investigated for clinical situations involving Helicobacter infections where it may have utility when administered alone and also when given in combination with established antibiotic agents.

Topics: Animals; Anti-Bacterial Agents; Cell Division; Clinical Trials as Topic; Disease Models, Animal; Gastritis; Helicobacter; Helicobacter Infections; Humans; Lactoferrin

The attachment of Helicobacter pylori to the human gastric mucosa is a complex process involving several specific structures recognised by the cell surface receptors. Sialylated multivalent high mol. wt glycoproteins have been shown to inhibit H. pylori sialic acid-specific haemagglutination. This study explored whether sialylated glycoconjugates from bovine milk could inhibit an experimental H. pylori infection in a mouse model. BALB/cA mice (6-8 weeks old) were inoculated with a mouse-passaged H. pylori strain 317p. Four weeks after infection the mice were given lactoferrin (iron-free LF or 20% iron-saturated LF) or bovine milk fat globule membrane fractions (MFGM or defatted MFGM) orally (400 mg/kg body weight) once daily for 10 days and then killed to examine for bacterial colonisation and gastritis. Mice treated with iron-free LF, 20% iron-saturated LF, MFGM or defatted MFGM showed 30%, 10%, 20% or 20% healing rates, respectively, when compared with the H. pylori-infected control. Gastric colonisation by H. pylori was remarkably decreased in all mice treated with bovine milk glycoconjugates and the inflammation score was also significantly lower in treated mice than in infected control animals. The fact that there was no significant difference between iron-free LF and iron-saturated LF or MFGM and defatted MFGM suggested that iron is not crucial for inhibition of H. pylori by lactoferrin and that the lipid part of MFGM is not important for anti-H. pylori activity. In conclusion, bovine milk glycoconjugates showed potencies to inhibit H. pylori infection in this mouse model and, therefore, could be considered as candidates for non-antibiotic strategies against H. pylori infection in man.

Topics: Animals; Cattle; Disease Models, Animal; Gastritis; Glycoconjugates; Helicobacter Infections; Helicobacter pylori; Lactoferrin; Mice; Mice, Inbred BALB C; Milk; Stomach

Recombinant human lactoferrin possesses in-vitro antibiotic and anti-inflammatory activity similar to the native form. It was tested for in-vivo activity in mice infected with the gastritis-inducing bacterium Helicobacter felis. A two-week course of treatment with lactoferrin was sufficient to partially reverse both infection-induced gastritis and the infection rate, and fully reverse gastric surface hydrophobicity changes. A comparison of lactoferrin with amoxicillin and standard triple therapy revealed no differences in infection rate. These results show that recombinant human lactoferrin is effective in a mouse model of Helicobacter infection, and support further testing of this promising agent for this application.

Topics: Amoxicillin; Animals; Body Weight; Dose-Response Relationship, Drug; Gastritis; Helicobacter; Helicobacter Infections; Humans; Lactoferrin; Mice; Mice, Inbred C57BL; Organ Size; Penicillins; Recombinant Proteins; Stomach; Time Factors

It remains unclarified whether bovine lactoferrin (bLF) can exert a therapeutic effect on the host infected with Helicobacter pylori.. Germfree BALB/c mice were orally inoculated with H. pylori to induce infection. Three weeks after infection the mice were given bLF orally once daily for 2 or 4 weeks and were then killed to examine the bacterial number in the stomach and the serum antibody titer to H. pylori. To count the number of epithelium-bound H. pylori, the resected stomach was agitated in phosphate-buffered saline to remove non-bound H. pylori before bacterial enumeration.. The administration of 10 mg bLF for 3 to 4 weeks decreased the number of H. pylori in the stomach to one-tenth and also exerted a significant inhibitory effect on the attachment of H. pylori to the stomach. As a result, the serum antibody titer to H. pylori, whose level is presumed to represent the size of the immune response by the host, thereby reflecting the degree of bacterial attack, decreased to an undetectable level.. These findings suggest that bLF exerts an inhibitory effect on colonizing H. pylori by detaching the bacterium from the gastric epithelium and by exerting a direct anti-bacterial effect.

Topics: Animals; Cattle; Enzyme-Linked Immunosorbent Assay; Gastritis; Germ-Free Life; Helicobacter Infections; Helicobacter pylori; Lactoferrin; Male; Mice; Mice, Inbred BALB C

Lactoferrin (Lf) is an iron-binding glycoprotein present in milk, lacrimae, saliva, and gastroduodenal secretions. In vitro studies disclosed contradicting results regarding the relation of Lf with Helicobacter pylori (HP) infection. This study aimed to investigate the relationship between the gastric mucosal concentration of Lf and HP infection of the stomach. The relationship of the gastric mucosal level of Lf with the gastric mucosal concentration of interleukin-8 (IL-8) and with the intragastric ammonia levels was also assessed. In addition, the gastric mucosal Lf levels before and after irradication of HP infection were also evaluated.. This study was composed of 27 HP-positive and 12 HP-negative patients with chronic gastritis. Gastric mucosal biopsy specimens were obtained from all subjects by endoscopy, and the degree of histological inflammatory changes were assessed according to the Sydney system. The gastric mucosal levels of Lf and IL-8 were measured by immunoassays. Assessment of the effect of therapy on the gastric mucosal level of Lf was performed in 10 patients with HP-associated duodenal ulcer.. Lf, IL-8, and ammonia levels were significantly higher in patients with HP-positive gastritis compared with those with HP-negative gastritis in both the antrum and the gastric body. Histologically, the degree of inflammatory changes correlated significantly with the Lf levels in the gastric mucosa. Furthermore, the degree of HP colonization was more significant in biopsy samples from the antrum than in those from the corpus of the stomach. The gastric mucosal levels of Lf and IL-8 correlated significantly in the antrum and the gastric body. The ammonia intragastric level significantly correlated with the mucosal Lf level in the antrum and in the gastric body. Therapy significantly decreased the Lf levels in the gastric mucosa of the antrum (p < 0.005) and the gastric body (p < 0.005).. The results of the present investigation showed, for the first time in vivo, that Lf concentration is increased in the biopsy specimens of patients with HP-related gastritis, and that the levels of Lf correlate significantly with the degree of inflammation of the gastric mucosa. The gastric mucosal level of Lf may constitute an excellent marker of HP infection.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Ammonia; Anti-Bacterial Agents; Anti-Ulcer Agents; Biomarkers; Biopsy; Chronic Disease; Clarithromycin; Duodenal Ulcer; Female; Follow-Up Studies; Gastric Juice; Gastric Mucosa; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Lactoferrin; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Pyloric Antrum

Recently, in vitro studies suggested that lactoferrin (Lf) might play an important role in the physiopathology of Helicobacter pylori-associated gastritis. However, whether Lf is present in the gastric juice and its relationship with H. pylori infection have not as yet been reported. In the present investigation the presence of Lf in gastric juice and its correlation with H. pylori infection were assessed.. This study comprised 30 H. pylori-positive and 14-negative patients with chronic gastritis. Gastric juice levels of Lf were measured with enzyme-linked immunoassays. Gastric juice concentration of Lf was also investigated in accordance with the histologic findings of biopsy specimens in the gastric body and antrum.. Lf concentration in gastric juice was significantly higher in H. pylori-positive than in -negative patients (P = 0.033). The pH values are known to influence the levels of Lf. However, intragastric Lf levels were also significantly increased in H. pylori-positive patients as compared with H. pylori-negative patients after correcting the Lf levels for pH values (P = 0.029) or after adjusting the pH values of the gastric juice with NaHCO3 solution in both groups of patients (P = 0.0007). In addition, the gastric juice levels of Lf correlated significantly with the gastric mucosal concentrations of Lf in the gastric body (P < 0.005, r = 0.568) and the antrum (P < 0.05, r = 0.401).. This study showed for the first time that Lf is present in gastric juice and that it correlates with H. pylori infection. Lf may constitute a good marker for H. pylori-associated gastritis. Although correlation does not prove causation, this study suggests that Lf might play an important role in the physiopathology of H. pylori-associated gastritis.

Topics: Biomarkers; Biopsy; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Gastric Juice; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lactoferrin

Topics: Antibody Formation; Biopsy; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulins; Lactoferrin; Lymphatic System; Muramidase; Plasma Cells

A total of 238 randomly selected gastric biopsies were examined with polyclonal antibodies from rabbits (antihuman-lysozyme and antihuman-lactoferrin) using the Peroxidase-Antiperoxidase-method according to Sternberger. The preparations were evaluated by comparing the intensity of the staining as well as the quantity and distribution of positive cells within the mucosa. The results show that lysozyme can be demonstrated constantly in the glandular neck zone and in the mucoid glandular body within the normal non-inflamed mucosa of the antrum, whereas in the normal corpus mucosa only a small amount of lysozyme appears focally and inconsistently in the neck area of the glands. A substantial increase in the intensity of lysozyme presentation due to inflammatory changes as related to the chronic superficial gastritis of the antrum cannot be discovered. On the contrary, the presentable amount of lysozyme decreases in line with the progressing inflammation and, in case of chronic-atrophic gastritis with intestinal metaplasia is restricted to the Paneth cells. A distinct and constant presentation of lysozyme can be achieved in the glandular neck zone, in the lower gastric pits and partially in the upper glandular body of the corpus mucosa in cases of chronic inflammatory processes. Obviously lysozyme is formed in the epithelial cells and not taken up from other cells. Furthermore it can be concluded from the findings that to a large extent lysozyme formation is linked to the proliferation activity of the epithelial cells. Lactoferrin cannot be found in normal non-inflammatory mucosa neither of the antrum nor of the corpus. But it can be found among most of the biopsy specimens with inflammatory changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Campylobacter Infections; Female; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Granulocytes; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Male; Metaplasia; Middle Aged; Muramidase

Biopsy specimens from Billroth-II-resected stomachs obtained endoscopically 28-32 years after the operation were subjected to an immunohistochemical study by two-colour immunofluorescence staining. The epithelial distribution of immunoglobulin A (IgA), secretory component (SC), lysozyme (Ly), and lactoferrin (Lf) was evaluated, and IgA-, IgM-, and IgG-producing cells were quantified in the lamina propria. Gastric body mucosa excised from resected stomachs obtained from patients with duodenal ulcer was used as control and showed considerably less extensive gastritis than the stump mucosa. Both specimen categories showed enhanced expression of epithelial IgA, SC, Ly, and Lf associated with severe gastritis, except for areas with intestinal metaplasia, which lacked Ly and Lf. The number of IgA-, IgM-, and IgG-producing cells was significantly increased with increasing degree of gastritis, particularly so for IgG cells on a relative basis. After partial gastrectomy, therefore, the stump mucosa generally responds with activation of local immune mechanisms; this response is principally similar to that seen in simple gastritis of comparable severity.

Topics: Adult; Female; Fluorescent Antibody Technique; Gastric Mucosa; Gastritis; Gastroscopy; Humans; Immunoglobulin A; Lactoferrin; Male; Middle Aged; Muramidase; Stomach; Time Factors

Epithelial distributions of immunoglobulin A, secretory component, lysozyme, and lactoferrin were studied by paired immunofluorescence staining in ethanol-fixed biopsy specimens from gastric antral and body mucosa. Fluorescence scores were assigned semiquantitatively for the epithelium in three mucosal zones (foveolar, isthmus, and glandular). In each case, degree of inflammation was graded blindly after conventional histologic staining of serial sections. The results showed that the overall epithelial expression of local defense factors was significantly enhanced in association with gastritis, both with regard to nonspecific antimicrobial substances (lysozyme and lactoferrin) and the external transfer of immunoglobulin A (mediated by secretory component) as a potential carrier of protective antibodies. The antral isthmus and glandular zones were most active in both respects. Despite the expression of relatively large amounts of epithelial immunoglobulin A and secretory component in metaplastic glands, these elements lacked the nonspecific defense factors (except for lysozyme in Paneth cells)--even when they occurred in the antral mucosa--and may, therefore, represent particularly vulnerable areas.

Topics: Adult; Aged; Female; Fluorescent Antibody Technique; Gastric Mucosa; Gastritis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Lactoferrin; Lactoglobulins; Male; Metaplasia; Middle Aged; Muramidase; Secretory Component; Staining and Labeling