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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 and immunologic dissonance: clinical implications

63%
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.
3

Lactoferrin regulates proliferative response of human peripheral blood mononuclear cells to phytohemagglutinin and mixed lymphocyte reaction

51%
Zimecki M., Stepniak D., Szynol A., Kruzel M. L.
Archivum Immunologiae et Therapiae Experimentalis
|
2001
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vol. 49
|
issue 2
147-154
EN
The aim of this study was to investigate the effects of bovine lactoferrin on the proliferative response of human blood lymphocytes induced by PHA and alloantigens in two-way mixed lymphocyte culture at a broad range of BLF concentrations (1.5 - 50 mug/ml). We found that the effects of BLF in both experimental models were differential and depended on an individual reactivity of lymphocytes with respect to mitogen or alloantigen and BLF concentration. Generally, lymphocytes from donors reactive to BLF exhibited higher proliferation indices compared to nonreactive individuals. Low BLF doses were regulatory and higher ones mostly inhibitory. MLR was in most cases inhibited by all doses of BLF, some MLR stimulated and other not affected by BLF. We conclude that basis for the differential action of BLF is its ability to sense the activation status of lymphocytes. The resultant effects of BLF are probably mediated by monocytes and cytokines.
4

Lactoferrin regulates the immune responses in post-surgical patients

39%
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.
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