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ABSTRACT: Polyphenols contained in red wine possess a broad array of properties which seem to be beneficial to human and animal health. We have investigated the ability of red wine polyphenols to promote the in vitro release of both proinflammatory and antiinflammatory cytokines from human healthy mononuclear cells, as well as of immunoglobulins from B cells. Following red wine (Negroamaro) pretreatment of lymphomonocytes, results will show a production of regulatory [Interleukin(IL)-12], proinflammatory (IL-1 beta and IL-6), and anti-inflammatory (IL-10) cytokines, as well as of IgA and IgG. The fine balance between inflammation and antiinflammation, as well as the role of humoral immune response either systemic or mucosal will be discussed as a consequence of red wine intake. Finally, since ageing is characterized by a decline of many immune functions, our results suggest that moderate use of red wine may be beneficial in age-related disorders where the host immune response is very often not effective against a variety of antigens.
Current pharmaceutical design 02/2008; 14(26):2749-57. · 4.41 Impact Factor
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ABSTRACT: Red wine represents a source of polyphenols which exhibit a number of biological effects on various systems. In this respect, there is evidence that red wine polyphenols constitute one of the ingredients of the Mediterranean diet which is associated to a reduced risk of coronary heart disease according to current literature. Here, we have evaluated in vitro the molecular mechanisms elicited by polyphenols from red wine (Negroamaro) on human healthy mononuclear cells. In particular, we have investigated the involvement of polyphenols in the activation of p38 and ERK1/2 molecules belonging to the MAPK kinase family and on the expression of I kappaB alpha and p65/NF kappaB. Results will demonstrate that in cells both the expression of p38 and ERK1/2 augments in the presence of red wine polyphenols, but their expression drops in the presence of polyphenols plus lipopolysaccharides (LPS). This indicates that in Gram-negative infections polyphenols may attenuate triggering of inflammatory mediators as a response to LPS stimulation. Finally, the regulatory role of polyphenols on I kappaB alpha and p65/NF kappaB expression is discussed, pointing out that red wine might favor anti-atherogenic mechanisms in the course of cardiovascular disease.
Current pharmaceutical design 02/2008; 14(26):2758-66. · 4.41 Impact Factor
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ABSTRACT: Many studies have been conducted on the effects of red wine polyphenols on certain diseases, primarily, coronary heart disease (CHD) and, in this respect, evidence has been demonstrated that intake of red wine is associated with a reduction of CHD symptomatology. In this framework, the purpose of this review is to illustrate the effects of polyphenols on immune cells from human healthy peripheral blood. Data will show that polyphenols are able to stimulate both innate and adaptive immune responses. In particular, the release of cytokines such as interleukin (IL)-12, interferon (IFN)-gamma, and IL-10 as well as immunoglobulins may be important for host protection in different immune related disorders. Another important aspect pointed out in this review is the release of nitric oxide (NO) from peripheral blood mononuclear cells (PBMC), stimulated by red wine polyphenols despite the fact that the majority of studies have reported NO production only by endothelial cells. Release of NO from PBMC may play an important role in cardiovascular disease, because it is known that this molecule acts as an inhibitor of platelet aggregation. On the other hand, NO exerts a protective role against infectious organisms. Finally, some molecular cytoplasmatic pathways elicited by polyphenols able to regulate certain immune responses will also be discussed. In particular, it seems that p38, a molecule belonging to the MAPK family, is involved in the release of IFN-gamma and, therefore, in NO production. All these data confirm the beneficial effects of polyphenols in some chronic diseases.
Current pharmaceutical design 02/2008; 14(26):2733-48. · 4.41 Impact Factor
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G M Lenato,
P Suppressa,
P Giordano,
G Guanti,
E Guastamacchia,
V Triggiani,
L Amati,
F Resta, V Covelli,
E Jirillo,
C Sabbà
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ABSTRACT: Hereditary Haemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome is an autosomal dominant disease characterized by local angiodysplasia affecting different organism districts. From a clinical viewpoint, HHT patients suffer from epistaxis, mucocutaneous telangiectases and arteriovenous malformations in various organs. Mutations in two known genes (ENG and ALK1) account for the majority of HHT patients. Additional loci are predicted, but the underlying genes are still to be identified. Moreover, SMAD4 mutations have been reported to cause JP-HHT combined syndrome. Both endoglin and ALK-1 bind to various growth factors in the context of the Transforming Growth Factors (TGF)-beta superfamily and their expression is restricted to vascular endothelial cells and very few other cell types, such as activated monocytes. Endoglin and ALK1 mutations are thought to affect endothelial cell metabolism, angiogenesis and vascular remodelling, even if the precise mechanism leading to the HHT lesions is still obscure. Endoglin is also overexpressed in smooth muscle cells of atherosclerotic plaques, suggesting a role for this protein in atherogenesis and plaque progression, as well as in other cardiovascular diseases. Recently, we demonstrated that HHT adult patients display several deficits of both innate and adaptive immune system. Here, we investigated the function of immune cells in HHT pediatric patients. Our results clearly show that HHT children have a normal functionally immune system, and suggest that HHT patients become immunocompromised host during their lifetime, likely due to a precocious immunosenescence. Moreover, the relationship between immune responsiveness in HHT and atherosclerosis are discussed.
Current pharmaceutical design 02/2007; 13(36):3656-64. · 4.41 Impact Factor
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ABSTRACT: 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.
Current pharmaceutical design 02/2007; 13(36):3718-25. · 4.41 Impact Factor
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Annals of the New York Academy of Sciences 12/2006; 741(1):216 - 222. · 3.15 Impact Factor
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ABSTRACT: Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel alterations such as dilatation of postcapillary venules and arterio-venous communications, which account for the major clinical manifestations of the disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively, depending the former on endoglin mutations and the latter on activin receptor-like kinase 1 (ALK-1) mutations. Both endoglin and ALK-1 bind to the transforming growth factor (TGF) superfamily which, physiologically, regulates the activities of endothelial cells and also those related to the extracellular matrix. In this review, the salient features of TGF-beta will be outlined with special reference to its activity on the immune system and on tumorigenesis. Furthermore, the involvement of TGF-beta in the pathogenesis of some gastrointestinal diseases will be discussed and, in particular, in the course of liver disease, Helicobacter pylori infection and inflammatory bowel disease. In the light of these data and of animal model of HHT, the potential risk of developing other diseases in HHT patients will be discussed.
Current Pharmaceutical Design 02/2006; 12(10):1195-200. · 3.87 Impact Factor
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ABSTRACT: In healthy individuals, natural and adaptive immune responses are able to control virus entry into the host. In particular, CD8(+)-mediated cytotoxicity, sustained by the intervention of CD4+ cells, represents the major key event leading to virus eradication. On the other hand, viruses are able to evade from host immune response via several mechanisms, and special emphasis will be placed on hepatitis C virus and chronic Epstein-Barr infections also in view of personal data. Virokines, viroreceptors, and serpins greatly contribute to viral immune escape, and, among virokines, interleukin (IL)-10 has been object of intensive studies. Finally, all these products have been used as biopharmaceuticals, and, for instance, viral IL-10, chemokine-binding proteins, and serpins exhibit in animal models immunosuppressive, anti-inflammatory, and antiatherogenic activities. As far as their use in human trials is concernded, many cautions are required in order to avoid deleterious side effects and, in particular, the purity of the product, its route and frequency of administration, as well as the immune status of the patient should be taken into serious account.
Current Medicinal Chemistry 02/2006; 13(3):325-33. · 4.86 Impact Factor
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ABSTRACT: Nowadays, calprotectin, a cytoplasmatic protein, released by activated neutrophilic polymorphonuclear cells (PMN) and/or monocytes-macrophages (MØ), is considered a good indicator of inflammation in several diseases. Accordingly, fecal calprotectin represents a good predictor of clinical relapse in ulcerative colitis (UC) patients, whereas conflicting results have been reported in Crohn's disease (CD) patients. In our study, in 76 IBD patients (29 CD and 47 UC) fecal calprotectin has been evaluated by a commercial ELISA kit. Results demonstrate that levels of this protein in the stool are significantly more elevated in active CD and UC patients than in normal volunteers. In quiescent CD and UC a trend to higher levels of calprotectin than in the normal counterpart is, however, evident. These data suggest that a low-grade inflammation of the intestinal wall is always present in CD and UC patients, which may predict a clinical relapse risk. In the same group of patients calprotectin levels also were analyzed according to sex and age. A trend to higher values of calprotectin was present in male patients with active or quiescent CD than in their female counterparts. Only in UC patients in remission a trend to calprotectin increase was more marked in the male group than in the female counterpart. When CD and UC patients were divided up according to age, calprotectin positivity peaked between 30-39 years in active CD patients, while in quiescent CD maximum positivity was between 40 and 49 years. However, in both active and quiescent UC patients, calprotectin positivity increased with age. The more precocious detectability of fecal calprotectin in CD patients, as a marker of intestinal mucosa inflammation, may be related to the different histopathology of the two diseases (CD versus UC). However, reduced PMN and/or MØ trafficking from peripheral blood to intestinal mucosa with age by effects of chronic treatment should not be ignored in CD patients.
Immunopharmacology and Immunotoxicology 02/2006; 28(4):665-81. · 1.83 Impact Factor
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ABSTRACT: It is well known that inappropriate nutrient intake accounts for the maintenance of the immunological equilibrium, in humans and animals. Vitamins, elements, lipids, proteins and nucleic acids play an important role in the regulation of cellular and humoral immune responses since single or multiple deficits of these food components have been shown to cause immune abnormalities. For instance, in the course of protein-calorie malnutrition bacterial and/or viral infections represent the major cause of death. Ageing is characterized by a decline of many immune functions, and this process is called immunosenescence. Here, we report novel findings on the inability of superantigens to activate old CD8+, natural killer and B cells, as an expression of cell amnesia. In the elderly, this lack of activation could lead to lethal effects in the case of severe staphylococcal infections. Quite interestingly, recent findings outlined some similarities between human immune deficiency virus (HIV)-1 infection and ageing in terms of immune changes. The model of HIV-infection may be useful for the interpretation of ageing mechanisms and possible therapeutical interventions. Finally, the role of nutrition in different pathological conditions and the use of medical foods for correcting of immune deficits will be described.
Current Pharmaceutical Design 02/2003; 9(24):1924-31. · 3.87 Impact Factor
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ABSTRACT: Several lines of evidence support a mutual relationship between the nervous system and the immune system. Therefore, it is not surprising that some neuropsychiatric disorders are also characterized by immune abnormalities. In patients with phobic disorders and in patients with migraine without aura some common immune abnormalities have been detected and, in particular, natural immunity deficits, exaggerated release of proinflammatory cytokines and circulating bacterial endotoxins have been found. In other neurological disease, some etiologic factors have been detected as in the case of Guillain-Barrè syndrome in which molecular mimicry between Campylobacter jejuni endotoxin and GM1 ganglioside may cause an acute inflammatory polyneuropathy. On the other hand, attempts to identify an antigen have been made in patients with Alzheimer's disease and schizophrenia. Finally, the chronic fatigue syndrome, an old illness in search for an antigen, risk factors and precipitating agents have been described but evidence for a specific antigen is still lacking.
Current Pharmaceutical Design 02/2003; 9(24):1951-5. · 3.87 Impact Factor
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ABSTRACT: Naloxone acts as an opioid antagonist, displacing opioid drugs from cellular receptors. Among opioid substances, beta-endorphins are able to bind to several cell receptors, even including those expressed by immune cells. In this respect, evidence has been provided that in the course of viral infections, as well as in patients with ulcerative colitis high levels of beta-endorphins are detectable. Here, peripheral blood lymphocytes (PBL) from 21 HCV infected patients and 14 patients with IBD, respectively, were incubated with Naloxone and Naloxone + Ca2+ in order to evaluate a putative modulation of PBL-mediated antibacterial activity. In fact, previous studies have demonstrated a reduction of this T-cell activity in HCV and IBD patients. In general terms, the above treatment led to a recovery of the depressed antibacterial activity. In some cases, increase in T lymphocyte function was obtained with Naloxone alone, while in other cases the combination Naloxone + Ca2+ gave rise to a restorative effect. Of note, in some instances, lymphocytes were unresponsive to pharmacological modulation. The overall results suggest that beta-endorphins may down modulate T-cell antibacterial response in HCV and in IBD patients by saturating peripheral receptors on immune cells. Therefore, it is likely that Naloxone and/or Naloxone + Ca2+ may displace opioid drugs, thus antagonizing their effects.
Immunopharmacology and Immunotoxicology 03/2001; 23(1):1-11. · 1.83 Impact Factor
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ABSTRACT: Psychoneuroimmunology is a growing scientific field which deals with the mutual interplay between nervous and immune systems. In this framework, many data have demonstrated that cytokines (CKs) derived from the periphery are able to cross the blood brain barrier and act upon the central nervous system (CNS) [e.g., the hypothalamic-pituitary-adrenal axis (HPAA)], thus regulating several physiological functions (thermoregulation, sleep, appetite) or damaging the nervous tissue, when released in exaggerated amounts. On the other hand, nervous cells, such as astrocytes and microglial cells also generate proinflammatory CKs which may be detrimental for the CNS. The neuromodulating CK network can be triggered by microorganisms and/or their products (i.e. bacterial endotoxins), but also stressful life events may activate the HPAA, thus affecting the immune system function. This review will place emphasis on some clinical conditions, such as phobia and migraine without aura (MWA), characterized by anxiety disorders. Patients affected by these neuropsychiatric alterations exhibit multiple functional deficits of phagocytes and T lymphocytes which allow penetration of various pathogens into the host. This is also supported by the detection of circulating bacterial endotoxins and the evidence of both spontaneous and induced exaggerated release of proinflammatory CKs in phobic and MWA patients. The possible iatrogenic effects of benzodiazepines (BDZ) on the immune system have been evaluated by in vitro and in vivo studies. In this respect, it emerges that diazepam exerts an inhibitory function on the immune system, while alprazolam behaves as an immunoenhancer. The presence of central and/or peripheral BDZ receptors on immune cells seems to be the key mechanism responsible for the immunomodulation exerted by these drugs.
Immunopharmacology and Immunotoxicology 06/1998; 20(2):199-209. · 1.83 Impact Factor
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ABSTRACT: Polymorphonuclear cells (PMN) and monocytes/macrophages (M/M) represent the first defence line against invading microorganisms. Both phagocytic cell functions are precociously compromised in human immunodeficiency virus (HIV)-infected subjects, thus leading to infectious and neurological complications in the late stages of disease. Among intracellular pathogens, emerging bacteria such as Bartonella henselae and Rhodococcus equi can cause peculiar clinical pictures, i.e. the bacillary parenchimal angiomatosis and a classical pyogranulomatous broncopneumonia, respectively. On the other hand, overproduction of proinflammatory cytokines (CKs) and, in particular, tumor necrosis factor-alpha under HIV or lipopolysaccharide stimulation may cause neural damage in terms of demyelination and subsequent development of acquired immunodeficiency syndrome (AIDS) dementia complex. Some therapeutical attempts have been made with colony stimulating factors in order to increase the number and potentiate the function of PMN and M/M. On the other hand, the use of drugs able to reduce exaggerated release of CKs by M/M is suggested in AIDS patients in order to prevent a further aggravation of the clinical condition.
Immunopharmacology and Immunotoxicology 06/1997; 19(2):147-64. · 1.83 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the effect of acute human corticotropin (ACTH)-releasing hormone (CRH) administration (100 micrograms, as i.v. bolus) on tumor necrosis factor-alpha (TNF alpha) levels in the inferior petrosal sinuses and in the peripheral blood of 7 patients with Cushing's disease subjected to diagnostic inferior petrosal sinus sampling. Blood samples for ACTH, beta-endorphin (beta-EPH) and TNF alpha were collected from inferior petrosal sinuses and periphery simultaneously. In addition, TNF alpha concentrations were measured after CRH administration (10 nmol/l, 100 nmol/l and 1 mumol/l) in culture medium from primary cultures obtained in 3 of 7 patients. At baseline, plasma ACTH and beta-EPH levels were significantly higher in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one and in the periphery (p < 0.001) whereas no significant difference was found as far as serum TNF alpha levels were concerned. CRH administration caused a significant increase of ACTH (p < 0.001), beta-EPH (p < 0.01) and TNF alpha (p < 0.01) levels greater in the ipsilateral inferior petrosal sinus than in the contralateral one and in the periphery. In addition, CRH increased ACTH, beta-EPH and TNF alpha levels in the culture medium of three ACTH-secreting tumors at the doses of 100 nmol/l and 1 mumol/l (greater than 300, 200 and 110% of baseline pretreatment incubation levels, respectively). These data suggest that CRH may increase TNF alpha concentrations in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma and in the peripheral blood as well. In addition, it stimulated TNF alpha release both in vivo and in vitro. These findings suggest the possibility that an imbalanced intrapituitary TNF alpha production can be detected in ACTH-secreting adenomas.
Neuroendocrinology 11/1996; 64(5):393-7. · 2.38 Impact Factor
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Annals of the New York Academy of Sciences 12/1994; 741:216-22. · 3.15 Impact Factor
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V Covelli
Annals of the New York Academy of Sciences 12/1994; 741:212-5. · 3.15 Impact Factor
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Annals of the New York Academy of Sciences 12/1994; 741:174-84. · 3.15 Impact Factor
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Annals of the New York Academy of Sciences 12/1994; 741:263-70. · 3.15 Impact Factor
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ABSTRACT: Complex and bidirectional relationships operate between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system (IS) and either in vivo or in vitro evidence supports a physiological role of the HPA axis-IS network. A part of the well-known pharmacological effects of glucocorticoid hormones (GC) as immunodepressive agents, the direct effects of many HPA axis hormones on IS functions are actually documented also in physiologic conditions. Conversely, numerous IS soluble mediators are reported to affect the HPA axis functions at various steps of HPA axis regulation, in both physiologic and pathologic conditions. Stress and aging may represent two paradigmatic conditions to show the relevance of the bidirectional network between HPA axis and IS, as in both HPA activation and IS impairment are frequently coexistent. Finally, in the context of the wide spectrum of HIV-related HPA axis abnormalities, a case of a Cushing's syndrome associated to an acquired immunodeficiency syndrome (AIDS-related complex) in a 24-year-old homosexual drug abuser is reported.
Acta neurologica 09/1994; 16(4):206-13.
