Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance

Togawa, Jun‐Ichi; Nagase, Hajime; Tanaka, Katsuaki; Inamori, Masahiko; Umezawa, Tadashi; Nakajima, Atsushi; Naito, Makoto; Sato, Shinobu; Saito, Toshifumi; Sekihara, Hisahiko

doi:10.1152/ajpgi.00331.2001

Cited by 95 publications

(76 citation statements)

References 39 publications

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“…4). It is reported that BLF causes the down-regulation of TNF-α and IL-1β and the upregulation of IL-10 via inhibition of the nuclear factor-κB pathway, which is involved in the regulation of many inflammation-associated genes [24]. TNF-α increases in synovial tissue and synovial fluid [20] and plays a pivotal role in the pathology of RA.…”

Section: Discussionmentioning

confidence: 99%

“…Intravenous or intraperitoneal administration of LF reduces the production of TNF-α and IL-6 in vivo [13,26]. Oral administration of bovine milk-derived LF (BLF) also decreases TNF-α and IL-6 production [25] and increases IL-10 production [24] in vivo. In the mouse collagen-induced and septic arthritis models, periarticular injection of human LF reduces inflammation [9].…”

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confidence: 99%

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Oral Administration of Lactoferrin Inhibits Inflammation and Nociception in Rat Adjuvant-Induced Arthritis

et al. 2004

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ABSTRACT. Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced µ-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inf lammatory effects, and also whether it modulates LPS-induced TNF-α and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injec ted paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-α production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the developme nt of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-α and upregulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Oral Administration of Lactoferrin Inhibits Inflammation and Nociception in Rat Adjuvant-Induced Arthritis

et al. 2004

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“…6,9,15 In the case of apo-lactoferrin, it has potential as a new therapeutic agent for inflammatory bowel disease. 56 It is important to say that apo-lactoferrin affects pathogens such as Salmonella enterica serovar Typhimurium and E. coli without inhibiting the growth of bifidobacteria. These data suggest that lactoferrin may have the potential to be combined with probiotic bacteria in biotherapeutic products, which could help to balance human gut microflora and limit the overgrowth of certain pathogenic microorganisms, 57 including parasites.…”

Section: Amoebicidal Effect Of Human Milk Is Due To the Protein Fractmentioning

confidence: 99%

Amoebicidal Activity of Milk, Apo-lactoferrin, sIgA and Lysozyme

León-Sicairos¹,

López-Soto²,

Reyes-López³

et al. 2006

Clinical Medicine & Research

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Entamoeba histolytica is a pathogenic, parasitic protozoan that can infect the large intestine and cause amoebiasis, an illness responsible for at least 100,000 deaths annually worldwide. The capacity of human milk to kill amoebas 6,15 and the amoebicidal action of secretory immunoglobulin type A (sIgA) 16 have been reported. However, it is unknown which other components of milk are amoebicides. As milk contains several microbicidal components, we fractionated milk and tested each fraction against trophozoites in axenic cultures to describe any amoebicidal effects of other components of human and bovine milk such as lactoferrin, lysozyme and sIgA. We also sought to identify any combined effect among these molecules. Objectives: To identify amoebicidal components in human milk and the effect of iron on the amoebicidal activity. Original ResearchDesign: Investigation in axenic cultures of Entamoeba histolytica trophozoites.Methods: Amoebas were treated with 5%-20% of human, bovine and swine milk, with 10% of human milk fractions (i.e., casein, proteins except casein and fat) or with 1 mg/ml of human milk apo-lactoferrin, human secretory immunoglobulin type A (sIgA) and chicken egg-white lysozyme (i.e., purified proteins). Milk proteins were detected using immunoblot. Confocal microscopy was used to define the interaction of milk proteins (100 µM each) and amoebas. Experiments were done at least three times in triplicate, and mean and standard deviations were calculated.Results: Human and bovine milk were amoebicidal showing a concentration-dependent effect. The amoebicidal effect was increased in the absence of iron. Milk protein fractions, with the exception of casein, were the components responsible for the amoebicidal activity found. Apo-lactoferrin, sIgA and lysozyme were identified in the amoebicidal milk protein fraction. Apo-lactoferrin showed the major amoebicidal effect. These proteins, either alone or in combination, showed a killing effect on the trophozoites.They bound to the amoebic membrane causing cell rounding, lipid disruption and damage. Conclusions:Milk proteins such as apo-lactoferrin, sIgA and lysozyme are able to kill Entamoeba histolytica trophozoites.This study confirms the importance of feeding breast milk to newborns.

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“…The mechanisms underlying the observed clinical improvement have not been fully elucidated but in cats it has been reported that, bovine lactoferrin can also reduce IFN-γ production by concanavalin A stimulated peripheral blood mononuclear cells [37]. Interestingly, related studies of intestinal inflammation in rats have also shown a clinical improvement following oral administration of bovine lactoferrin and this was associated with an enhanced production of IL-4 and IL-10 and a reduction in TNF-α, IL-1β and IL-6 [53].…”

Section: Mucosal Cytokines and The Response To Mucosal Infectionmentioning

confidence: 99%

Mucosal defence along the gastrointestinal tract of cats and dogs

Stokes

Waly

2006

Vet. Res.

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-Diseases that are associated with infections or allergic reactions in the gastrointestinal and respiratory tracts are major causes of morbidity in both cats and dogs. Future strategies for the control of these conditions require a greater understanding of the cellular and molecular mechanisms involved in the induction and regulation of responses at the mucosal surfaces. Historically, the majority of the fundamental studies have been carried out in rodents or with tissues obtained from man, but the expanding range of reagents available for the study of farm and companion animals provides opportunities for study in a wider range of animals including cats and dogs. To date, these studies have tended to be focussed on characterising the cellular distributions in healthy animals and in groups of cats and dogs identified as having an increased risk of mucosal disturbance. Where species comparisons of mucosal immune systems have been made, the results have tended to be divided between monogastric and ruminant animals. It is then not surprising that the mucosal immune systems of both cats and dogs bear greatest similarity to that documented for man and pigs.

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Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance

Cited by 95 publications

References 39 publications

Oral Administration of Lactoferrin Inhibits Inflammation and Nociception in Rat Adjuvant-Induced Arthritis

Oral Administration of Lactoferrin Inhibits Inflammation and Nociception in Rat Adjuvant-Induced Arthritis

Amoebicidal Activity of Milk, Apo-lactoferrin, sIgA and Lysozyme

Mucosal defence along the gastrointestinal tract of cats and dogs

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