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1

Role of lactoferrin in development of inflammation

100%
Kruzel M. L.
Postępy Higieny i Medycyny Doświadczalnej
|
2003
|
vol. 57
|
issue 4
377-404
EN
During acute inflammation, immune homeostasis is lost leading to destructive immunopathology. Homeostasis is normally dependent upon coordinated interactions among the various lymphoid, phagocytic and somatic cells that comprise the immune system. In general, these interactions are tightly regulated to obtain a balance between mechanisms necessary to eliminate harmful pathogens, and overaggressive responses leading to destruction of host tissue. Activation of immunoeffector cells results in pro-inflammatory cytokine up-regulation which in turn also activates the vascular endothelium. Through complex signaling, a positive feedback circuit is established which amplifies and sustains the activity of the inflammatory response resulting in the release of other cytokines and related molecules. If these responses are activated in an uncontrolled fashion with dissemination via the circulation, over the period of time, organs distant from the initial insult can be affected to produce multiple organ failure. Lactoferrin, an iron-binding glycoprotein, is considered an important mediator in host defense against the environmental insults in mammals. By virtue of iron sequestration lactoferrin can control the development of many oxidative stress-driven responses. The purpose of this review is to provide a comprehensive summary of research regarding lactoferrin and its role in homeostasis.
2

Lactoferrin regulates production of interleukin-6 and tumor necrosis factor alpha in mice

100%
Machnicki M.
Postępy Higieny i Medycyny Doświadczalnej
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1995
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vol. 49
|
issue 1
53-57
3

Lactoferrin regulates the immune responses in post-surgical patients

80%
Zimecki M., Wlaszczyk A., Wojciechowski R., Dawiskiba J., Kruzel M., Kruzel M. L.
Archivum Immunologiae et Therapiae Experimentalis
|
2001
|
vol. 49
|
issue 4
325
EN
The effect of oral administration of lactoferrin (LF) was studied to determine if it could modify post-surgical immune response. The action of lactoferrin was evaluated in 18 LF-treated patients versus 28 placebo counterparts. Patients (women and men, mean age 50 years) were given daily oral doses (20 mg each) of LF for 5 consecutive days prior to thyroid surgery. The following immune response parameters were determined in blood samples taken from the patients one day before, one day after, and 5-7 days following surgery: cell morphology, the proliferative response of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), and the spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor alpha (TNF-) and interleukin 6 (IL-6). As a consequence of the thyroid surgery, the total leukocyte count increased on the postoperative day by about 50% in all patients and the percentage of lymphocytes fell by 26 and 35% in the control vs LF-treated group. The content of neutrophils, on the other hand, elevated on day 1 post-operation by 51 and 68%, respectively. The percent of neutrophil precursors was markedly higher in LF-treated patients, particularly on the day before and the day after surgery (4.1 and 4.8 vs 2.5 and 3.7%, respectively). The post-surgical values were, however, comparable in both groups for neutrophils. The proliferative response of lymphocytes showed a slight decrease in the control group and an increase in the LF-treated patients on day 5 post-operation (20% over control group). LPS-induced TNF- production was higher in LF-treated patients in both one day before and one day following surgery (28 and 24% respectively). LPS-induced IL-6 production was comparable in both placebo and LF-treated patients before surgery, however, on day 1 and 5 following surgery, the production of IL-6 was higher in LF-treated patients by 65 and 27%, respectively. Taken together, the data presented in this study revealed increased immune responsiveness in all patients treated with lactoferrin subjected to the thyroid surgery. This suggests that treatment with lactoferrin could constitute an effective protective measure against post-surgical complications.
4

Lactoferrin and immunologic dissonance: clinical implications

80%
Kruzel M. L., Zimecki M.
Archivum Immunologiae et Therapiae Experimentalis
|
2002
|
vol. 50
|
issue 6
397-408
EN
Homeostasis is the maintenance of equilibrium in a biological system by means of positive and negative feedback control mechanisms that counteract influences tending toward physiological dissonance. At the molecular level, homeostasis is controlled by the network of the neuro-endocrine-immune system, in which lactoferrin plays a central role. The purpose of this review is to provide a comprehensive summary of a collaborative study established between the Hirszfeld Institute of Immunology and Experimental Therapy (Wroclaw, Poland) and the University of Texas Health Science Center (Huston, USA) regarding lactoferrin and its role in homeostasis. In our studies we focused on the immunoregulatory functions of lactoferrin, both in vitro and in vivo. We investigated the immune status of individuals subjected to different insults, including experimental endotoxemia in mice and surgery in humans. We also studied a lactoferrin-dependent delayed type hypersensitivity (DTH) response to evaluate some of the mechanisms by which lactoferrin can effectively substitute an adjuvant in vaccine.
5

Reconstitution of the cyclophosphamide-induced, impaired function of the immune system in the animal models

80%
Artym J.
Postępy Higieny i Medycyny Doświadczalnej
|
2003
|
vol. 57
|
issue 1
55-66
EN
Cyclophosphamide (CY) is an alkylating agent used in chemotherapy of tumors and autoimmune disorders. The drug causes a large number of side-effects including deep, transient lymphopenia and neutropenia, thus rendering the immune system susceptible to infections. In this review we focus on the effects of CY on the haematopoietic system and the immune response in rodents. In addition, we present approaches aimed at reconstitution of lympho- and myelopoiesis using a spectrum of immunotropic factors including: thymic hormones, cytokines, low-molecular weight compounds, bacterial products and lactoferrin.
6

Lactoferrin stimulates killing and clearance of bacteria but does not prevent mortality of diabetic mice

70%
Zagulski T., Jarzabek Z., Zagulska A., Jaszczak M., Kochanowska I. E., Zimecki M.
Archivum Immunologiae et Therapiae Experimentalis
|
2001
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vol. 49
|
issue 6
431-438
EN
We have previously shown that bovine lactoferrin (BLF) given intravenously (i.v.) protected mice against a lethal dose of E. coli and strongly stimulated both the clearing and killing activities in liver, lungs, spleen and kidney. Since some studies indicated a reduction of the manifestation of experimental pancreatitis with lactoferrin, we decided to examine the protective activity of BLF against lethal E. coli infection in animals with alloxan (Alx)-induced diabetes. It appeared that 48 h diabetes substantially lowered the killing activity in all four organs as well as the clearing rate of E. coli from the circulation. BLF given i.v. o reduced this undesirable effect of diabetes. However, in 10- and 20-day diabetic animals, the diabetes alone stimulated the killing activity in the organs investigated, and upregulated the clearing rate of E. coli from the circulation. Lactoferrin (LF) significantly increased both the killing and the clearing activity in these long-term diabetic animals. In some cases the stimulating effect of BLF was very high, suggesting a concerted action of BLF and diabetes in that category of mice. Despite these beneficial effects of BLF and diabetes on the killing process in the investigated organs, the survival time of animals from all the diabetic groups ( 48 h, 10 and 20 days) was not prolonged by BLF. The protective properties of BLF did not depend on the blood glucose levels in the diabetic animals. BLF partly delayed the development of experimental Alx-induced diabetes, measured by the glucose level, but only if administered shortly after Alx injection. In conclusion, we demonstrated that the state of diabetes alone could increase killing of bacteria in the investigated organs and LF enhanced this process. However, LF had no protective effect against the mortality of diabetic mice infected with a lethal dose of E. coli.
7

Time-dependent observations of secretion marker levels in nasal secretion after histamine and methacholine provocations

61%
Pupek M., Mikulewicz W., Mielnik J., Batycka B., Katnik-Prastowska I.
Archivum Immunologiae et Therapiae Experimentalis
|
2003
|
vol. 51
|
issue 4
259-265
EN
Nasal provocation tests with histamine and methacholine were carried out in 25 healthy men on an effort to assess the dynamic changes of albumin, total IgA, secretory IgA and lactoferrin concentrations in the nasal secretion. The trials were performed with 0.5, 1, and 4 mg of histamine and 8, 16, 32 mg of methacholine. Each dose of histamine or methacholine was sprayed into a nose every second day, and with two days interval between two provocating agents. The nasal secretions were collected after saline spraying only forming baseline group and after 3, 10 and 15 minutes of the challenge agent administration. The baseline levels presented the following values: for albumin 257? 230 mug/ml, secretory IgA 608 ? 379 mug/ml, total IgA 1025 ? 423 mug/ml, and lactoferrin 213 ? 156 mug/ml. The increase of albumin level after nasal provocation, particularly significant after histamine administration (to 3713 ? 2311 mug/ml), indicates the incessant protein plasma leaking from the blood circulation to the nasal secretion. After administration of both provocating agents there was the significant gradual decrease of secretory IgA level, even below the baseline value. After the 2nd and the 3rd doses of methacholine and histamine spraying the concentration of secretory IgA decreased 2-3 times and was found to be 200-300 mug/ml, respectively. Also, lactoferrin concentration values decreased gradually after the 2nd and 3rd doses of methacholine and histamine to level close the baseline value. These observations suggest time and dose dependent, a non-specific dysfunction of local immunity response after nasal provocations.
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