Dr. Barbara Tonin
PREMISE
he immune response is of primary importance in the pathogenesis of canine leishmaniosis and a protective role against this infection is given by the cell-mediated response (Th1). Animal studies have confirmed the positive effect of the Th1 response (IFN-γ, IL-12, TNF-α), compared to Th2 (IL-4, IL-5, IL-10), in the treatment or the progression of the disease (Coffman et al, 1991; Reiner et al, 1995).
Similarly, there was a reduced monocyte activation and cell-mediated response in dogs infected by leishmaniosis compared to healthy subjects (Barbieri, 2006).
It is therefore logical, consider that the administration of immune-stimulating substances may affect the outcome of therapy and so the prognosis of the disease.
ZINC AND IMMUNE RESPONSE
Zinc is a trace element ubiquitous in the body, essential to many body functions and essential for proper functioning of the immune system (Haase et al, 2008)
| Zinc functions |
| DNA replication |
| RNA transcription |
| Signal transduction |
| Enzyme catalysis |
| Adjusting oxide reduction reactions |
| Cell proliferation and differentiation |
| Cellular apoptosis |
Table 1: Biological functions Zinc-related (Overbeck et al, 2008)
The immunological effects of zinc deficiency are multifactorial since they involve the synthesis of proteins and nucleic acids, the production of thymic hormones, stimulation of the activity of T lymphocytes, the stabilization of cell membranes and the function of the phagocytic cells.
Decreased activity of the line monocyte / macrophage, granulocyte phagocytosis and impaired cytotoxic activity are common consequences of zinc depletion (Ibs and Rink, 2003).
ZINC AND CELL-MEDIATED RESPONSE
The T cells are undoubtedly the most sensitive immune cells to zinc depletion and in case of deficiency is impaired their proliferation and subsequent differentiation of Th1 (Fraker and King, 2004; Overbeck et al, 2008).
For those reasons should not be underestimated those conditions can alter the homeostasis of this important trace element.
- Causes of hypozincemia
First of all a state of hypozincemia can result from inadequate dietary intake.
The zinc absorption is significantly reduced in the presence of foods rich in phytates (poor diets or with a high content of whole grain) or with excessive calcium supplementation, mineral can interfere with the absorption of organic zinc salts.
In addition, a condition of hypozincemia may occur in patients in races with absorption defects or suffering from chronic inflammatory conditions, where there is a liver seizure of micro-element (Philcox et al, 1995).
Therefore the integration utility of zinc on the immune response in infectious diseases, can be derived not only for the multitude of biological functions in which it is involved, but also for the widespread prevalence of conditions in which occurs a subclinical deficiency of this mineral (Haase et al, 2007).
| Disease | Effect of the administration of Zinc |
| HIV/AIDS | Reduction of opportunistic infections |
| C Hepatitis | Better response to treatment with IFN-α; decreased gastrointestinal symptoms |
| Shigellosis | Lymphocyte proliferation; increased antibody titers |
| Tuberculosis | Increased plasma retinol; reduction of healing times in skin lesions |
| Acute respiratory infections | Decrease morbidity; reduction of hospitalization time |
| Helicobacter pylori | Better response to antibiotic therapy |
Table 2: Zinc therapy in human infectious diseases (Haase et al, 2007; Overbeck et al, 2008)
ZINC AND LEISHMANIA
The close relationship between immune response and leishmaniasis has highlighted the role of substances with immunostimulant properties that could affect the progress of the disease.
- Leishmania and immune response
The role of zinc in the infection by Leishmania is being studied as the outcome of infection is closely related to the type of immune response that is triggered.
In particular the control of infection or the evolution of the disease, depend on the phenotype of activated T lymphocyte helper (Th1) and the production of IFN-γ, IL-2, TNF-α by Th1 cells is associated with the resolution of ‘ infection, and then the protection of the infected subjects.
In the dog population infected subjects with clinically manifested disease, show a predominantly humoral immune response and not protective disease (Th2-like), while the infected individuals who do not develop the disease show a predominantly cellular immune response and protective (Th1-like) (Barbieri , 2006).
The substances produced by Th2 lymphocytes do not protect the body from the aggression of leishmania infection since they refer to the departure site of immature macrophages with reduced potential pesticide. It follows a systemic spread and persistence of leishmania “protected” within macrophages, which stimulate the humoral response (non-protective) determine an immunopathological state, characterized by the production of circulating immune complexes (Ic).
- Zinc, cell-mediated response and Leishmaniasis
The integration of zinc, stimulating the generation of Th1 response, it may therefore affect the strength and the progression of the disease since the success of host resistance is depending on the activity of the macrophages stimulated by cytokines and IFN-γ produced by Th1 cells . Conversely zinc deficiency determines a shift of Th1 / Th2 ratio and consequent decrease of IL-2, IFN-γ and TNF-α (Beck et al, 1997).
- Hypozincemia and Leishmaniosis
Low plasma zinc concentrations were in fact observed in patients with mucosal and visceral Leishmania (Van Weyenbergh et al, 2004). Otherwise, subject normal-zincemical, following the oral administration of the micro-element, presented a self-limiting or moderate form of the disease (Sharquie et al, 2001). These results therefore seem to corroborate the correlation between concentration of zinc and immune anti parasitic response.
- Anti-leishmanial Zinc effect?
The zinc interest in the pathogenesis of Leishmania has also led to the direct study of the effect of this trace element on the proliferation of the parasite. From the results of research conducted in vitro, it would appear an anti-leishmaniale effect of the inhibition of enzymes resulting zinc parasitic involved in glucose metabolism (Najim et al, 1998 – Al-Mulla Hummadi et al, 2005).
The study of Najim et al (1998) was also shown a prophylactic effect in the onset of skin Leishamaniosi following the oral administration of zinc. The group of animals that had received zinc, immediately after infection with parasites of Leishamania and within 5 days, showed a dose-dependent reduction of skin lesions than untreated subjects.
Zinc: protective and therapeutic role
In conclusion, administration of zinc may constitute not only an important therapeutic aid of canine leishmaniosis, but primarily a prevention in the subjects most at risk of infection. For this purpose, it should be evaluated zinc supplementation in all immunosuppressed individuals living in endemic areas or for those who attend occasionally these areas.
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