Felicita Jirillo

Immunological properties of donkey's milk: its potential use in the prevention of atherosclerosis.

Donkeys milk is the best substitute of human milk for its content in lactose, proteins, minerals, and omega-3 fatty acids. Here, we have evaluated the effects of colostrum and milk from donkeys (Martina Franca breed) on the function of human peripheral blood mononuclear cells (PBMCs) at different intervals from lactation. Colostrum induced more IgA responses, while milk induced predominantly more IgG responses. Both milk and colostrum induced expression of CD25 and CD69 on PBMCs. The ability to induce release of interleukins (IL) (IL-12, IL-1 beta and IL-10) and tumor necrosis factor-alpha was confined only to milk, while colostrum was devoid of this capacity. Finally, both colostrum and milk induced nitric oxide (NO) release from PBMCs but milk exhibited a greater capacity than colostrum in NO generation. Taken together, these immunological activities exerted by both colostrum and milk from donkeys may be useful in the treatment of human immune-related diseases. In particular, NO induction by donkeys milk may be very useful in the prevention of atherosclerosis, being a strong vasodilator and an effective antimicrobial agent since pathogens and/or their products may play a proatherogenic role.

Donkey's and Goat's Milk Consumption and Benefits to Human Health with Special Reference to the Inflammatory Status

The environmental impact as well as malnutrition are responsible for an increased incidence of inflammatory diseases with a consequential loss of immune homeostasis. Therefore, administration of nutraceuticals is aimed at reconstituting the immune balance in terms of the so-called immune nutrition. Among many known nutraceuticals, more recently, donkeys and goats milks have been used as good alternatives to human and bovine milk in various clinical conditions such as allergy, atopy and inflammatory diseases. In fact, both milks possess immunomodulating capacities and release nitric oxide, a potent vasodilator endowed with anti-atherogenic properties. In this review, emphasis will be placed on the consumption of fermented milk and, in particular, on its ability to modulate the aged immune system, even including the intestinal mucosal immune response in elderly. Therefore, for their specific properties donkeys and goats milk administration to aged people should be encouraged.

Donkey and Goat Milk Intake and Modulation of the Human Aged Immune Response

In a group of 14 healthy aged subjects, donkey and goat milk was administered respectively, for a period of one month. Cytokine profile [interleukin (IL)-12, IL-10, IL-1beta, IL-8, IL-6 and Tumor Necrosis Factor (TNF)-alpha] was assessed before and after milk intake by means of a cytometric bead array test. Data demonstrated that IL-12 was undetectable, while IL-10, IL-1beta and TNF-alpha were released in very low amounts. Quite interestingly, IL-8 was increased by donkey milk administration, while same cytokine was dramatically decreased following goat milk intake. Same pattern of response was noted with IL-6 even if levels of these cytokine were lower than those detectable in the case of IL-8. Taken together, these findings indicate that administration of donkey milk in the aged host is able to upregulate the immune response, while goat milk seems to reduce the exaggerated acute phase response in elderly.

Healthy Effects Exerted by Prebiotics, Probiotics, and Symbiotics with Special Reference to their Impact on the Immune System

Pre-, pro-, and symbiotics are endowed with a broad spectrum of beneficial effects when administered to animals and humans. A series of experimental and clinical studies have clearly demonstrated that prebiotics, probiotics, or their combination are very effective in attenuating chronic inflammatory conditions such as inflammatory bowel disease or obesity. In addition, these natural products are able to prevent or arrest tumor development, acting on the intestinal microbiota as well as potentiating the immune response.Aging is characterized by a dramatic reduction of both innate and adaptive immune responses, the so-called immunosenescence. This leads to an increased incidence of infections, autoimmune diseases, and cancer in the elderly. Pre-, pro-, and symbiotic administration has been shown to ameliorate the immune response in aging. In particular, administration of a symbiotic to free-living elderly was able to potentiate the release of interleukin-8, thus increasing neutrophils in the host, perhaps explaining the reduced frequency of winter infections in the elderly.

Anti-inflammatory and anti-allergic properties of donkey's and goat's milk.

Nowadays, donkeys and goats milk consumption has been reevaluated for its potential benefits to human health. For example, in infants with intolerance to cows milk, donkeys milk represents a good alternative due to its chemical characteristics similar to those of human milk. On the other hand, goats milk in virtue of its higher content in short chain, medium chain, mono and polyunsaturated fatty acids than that of cows milk, is more digestible than the bovine counterpart. From an immunological point of view, donkeys milk is able to induce release of inflammatory and anti-inflammatory cytokines from normal human peripheral blood lymphomononuclear cells, thus maintaining a condition of immune homeostasis. Similarly, goats milk has been shown to trigger innate and adaptive immune responses in an in vitro human system, also inhibiting the endotoxin-induced activation of monocytes. Finally, in these milks the presence of their own microbiota may normalize the human intestinal microbiota with a cascade of protective effects at intestinal mucosal sites, even including triggering of intestinal T regulatory cells. In the light of the above considerations, donkeys and goats milk should be recommended as a dietary supplement in individuals with inflammatory and allergic conditions, even including elderly people.

Reactive Oxygen Species (ROS): involvement in bovine follicular cysts etiopathogenesis

Ovulation is compared to an acute inflammatory process during which vasoactive agents, prostanoids, leukotrienes and Reactive Oxygen Species (ROS) develop. The aim of this study was to evaluate the levels of ROS in cystic and follicular fluid, in order to establish their involvement in the etiopathogenesis of Cystic Ovarian Follicle (COF) in dairy cows. The study was conducted in 30 healthy cows (group C) and 30 cows affected by COF (group COF). The fluid of follicular cysts and of preovulatory follicles was drawn by means of ultrasound guided aspiration from the cows of both groups. The fluid obtained was analyzed by a photometric analytical system to detect ROS level. ROS concentration was statistically lower in the cystic fluid than in the follicular one (62.4 ± 13.36 U.Carr vs. 84.89 ± 26.99 U.Carr) (p<0.05), thus suggesting that an alteration of the cascade responsible for ROS production may be implicated in the complex etipathogenesis of COF.

Maturation of fish erythrocytes coincides with changes in their morphology, enhanced ability to interact with Candida albicans and release of cytokine-like factors active upon autologous macrophages.

Erythrocytes from the rainbow trout Salmo gairdneri Richardson (Salmo g.R.) were classified into immature and mature populations, respectively, by measuring longitudinal diameters. More elongated fish erythrocytes (FE), classified as mature cells, were those interacting with Candida albicans (CA) in a higher frequency in terms of either binding to the fungus or its intracellular engulfment. At the same time, in the rosetting phenomenon more elongated mature FE surrounded macrophages (MØ) phagocytosing CA. Finally, FE activated by CA released in the supernatants cytokine‐like factors able to modulate MØ functions. In particular, these active supernatants were analyzed for their capacity to inhibit MØ migration Macrophage Inhibition Factor (MIF) activity and enhance MØ phagocytosis. Both activities were detected in supernatants from CA stimulated FE but not in control supernatants. MIF activity could play a role in the accumulation of MØ in the context of functional rosettes, while the factor enhancing MØ phagocytosis could promote clearance of CA in a more efficacious way.

Antigenically Activated Avian Erythrocytes Release Cytokine-Like Factors: A Conserved Phylogenetic Function Discovered in Fish

Fish erythrocytes are endowed with the ability to produce cytokine like factors when stimulated with Candida albicans (Ca). To evaluate whether similar activities are still conserved in bird erythrocytes (BE), a morphological, cytochemical and immunological evaluation was conducted on peripheral cells in chickens (Gallus gallus). BE form rosettes with monocytes (Mo)-macrophages (MØ), and Mo-MØ according to cytochemical analysis to maintain phagocytic functions across the evolution. Finally, Ca-activated BE release in the supernatants cytokine like-factors that enhance Mo-MØ phagocytosis (interferon-γ-like activity) and inhibit Mo-MØ migration in agarose (migration inhibitory factor activity). In conclusion, bird erythrocytes, as nonimmune cells, are able to participate in the immune response contributing to the host defence.

First Demonstration of an Increased Serum Level of Reactive Oxygen Species During the Peripartal Period in the Ewes

Reactive Oxygen Species (ROS) are produced during oxidative metabolism, and regulate many biological processes. The acute inflammation characterizing parturition induces many physiological changes. Among them, there is evidence that ROS affect the synthesis of many factors involved in parturition. Our study aims to determine serum levels of ROS in periparturient ewes, as well as to establish a value of reference of their physiological concentration. ROS determination was performed on blood collected every 12 hours in periparturient twin pregnant ewes. Our results will show a significant increase in ROS concentrations from the beginning to the end of the experiment. This increase may be due to the inflammatory process establishing during parturition.

Red Wine Consumption and Prevention of Atherosclerosis : An In Vitro Model Using Human Peripheral Blood Mononuclear Cells

Evidence has been provided that red wine possesses antiatherogenic activities in virtue of its content in polyphenols (flavonoids and non-flavonoids substances). Here, some red wines (Negroamaro, Primitivo and Lambrusco) were tested for their ability to trigger nitric oxide (NO) production from human healthy peripheral blood mononuclear cells (PBMC). Negroamaro was the strongest inducer of NO from PBMC and deprivation of polyphenols did not influence its NO generation capacity. This fact supports the involvement of polyphenols in the NO production even in the absence of alcohol, which also per se does not exert any significant activity. These results are also corroborated by the evidence that PBMC inducible-nitric oxide synthase expression occurred by the effect of samples containing polyphenols but this expression was very weak when polyphenols were removed from the whole Negroamaro. In synthesis, flavonoids and resveratrol, major constituents of red wine, once absorbed at intestinal level, enter circulation and trigger monocytes for NO production. To the best of our knowledge, this is the first demonstration of a direct effect of red wine on monocytes for NO release to occur. On the other hand, also the macrophage contingent from gut-associated lymphoid tissue can contribute to NO generation, besides the aliquot produced by endothelial cells, as previously demonstrated by various authors. Taken together, these results support the concept that moderate intake of red wine can prevent atherosclerosis via production of NO, a potent vasodilator of terminal vessels.