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Biomedical subjects

E Jirillo

Publications and source records attributed to E Jirillo.

At least 73 records · Page 4Linked to original sources
PubMed1997

In vitro effects of recombinant human granulocyte-macrophage colony-stimulating factor (RhGM-CSF) on polymorphonuclear cell (PMN) and monocyte (MO) functional capacities in ovarian cancer patients versus human volunteers.

Human polymorphonuclear cells (PMN) and monocytes (MO) from four ovarian cancer patients and seventeen normal donors were in vitro pretreated with different concentrations (25, 50 and 100 IU, respectively) of rhGM-CSF. Phagocytosis and killing of PMN and MO as well as PMN polarization were evaluated in cancer patients before treatment (T0) and at the end of each chemotherapeutic cycle (T1, T2, T3 and T4, respectively) in comparison with normal donors. RhGM-CSF did not affect phagocytosis and killing of PMN and MO. On the other hand, this cytokine was per se endowed with the capacity to enhance PMN polarization in both cancer patients (at T2 interval) and normal donors.

Aged↗
PubMed1997

Role of lipopolysaccharide and related cytokines in Helicobacter pylori infection.

Helicobacter pylori is a gram-negative bacterium which accounts for the development of chronic gastritis and peptic ulcer in man. In this review, emphasis has been laid on the role of lipopolysaccharide (LPS) of the H. pylori cellular wall in the pathogenesis of gastroduodenal disease. H. pylori LPS exhibits a reduced endotoxic potency in terms of pyrogenicity, lethality, toxicity, mitogenicity, cytokine (CK) release and chromogenic limulus amebocyte lysate assay. This low biological activity of the LPS could be ascribed to the underacylation and underphosphorylation pattern of the lipid A backbone. However, also LPS core structures seem to contribute to the biological activity of the molecule. Despite this low immunological potential, an array of proinflammatory CKs are produced both in vitro and in vivo following stimulation of mucosal cells with H. pylori organisms. It is likely that LPS plays a major role in triggering interleukin (IL)-8, IL-1 and tumor necrosis factor-alpha production from both epithelial cells and macrophages. Finally, the lower immune response elicited by H. pylori LPS in comparison with other enterobacterial LPS may represent an escape mechanism from the host immunosurveillance exerted by this bacterium, thus allowing its survival and persistence in the gastric niche.

Animals↗
PubMed1997

CD45RA and CD45RO isoform expression on intrahepatic T-lymphocytes in chronic hepatitis C.

A liver tissue recruitment of antigen-specific cytotoxic cells has been reported in chronic hepatitis C virus (HCV) infection, but whether they really play a role in viral clearance is still a matter of investigation. To further evaluate T-cell involvement in HCV-induced hepatic disease, the authors analysed, in a cohort of chronic hepatitis C patients, the intrahepatic T-cell expression of CD45 isoforms by using specific monoclonal antibodies. Within hepatic specimens, CD45RA+ (naive) cell frequency at the portal tract level was significantly higher than that exhibited at lobular level. At the same time, a large number of CD45RO+ (memory) cells was found at periportal sites in comparison with the lobular counterpart. The evaluation of CD45RA and CD45RO isoform topographical distribution in relation to CD4+ and CD8+ lymphocytes, as determined on serial sections, showed that CD45RA antigen expression was predominantly coexpressed with CD4+ lymphocytes at the portal tract level, and the CD45RO phenotype with CD8 structure at the lobular and periportal sites. The levels of CD45 isoforms did not show any correlation with biological and/or histological disease activities. The results suggest that a liver recruitment of both naive and memory cells occurs during chronic HCV infection, even if their functional role needs to be further clarified.

Adolescent↗
PubMed1996

Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats.

Vascular reactivity and activation of the nitric oxide (NO) pathway were investigated in perfused mesenteric vascular bed removed from rats 5 h after i.p. injection of bacterial lipopolysaccharide (E. coli lipopolysaccharide, 30 mg kg -1). Lipopolysaccharide treatment induced hyporesponsiveness to noradrenaline. Maximal noradrenaline-induced vasoconstriction was significantly reduced in lipopolysaccharide-treated vs. untreated preparations. Continuous infusion of L-arginine (L-Arg) (0.2 mM) enhanced noradrenaline hyporeactivity of lipopolysaccharide-treated rats. N omega-Nitro-L-arginine methyl ester (L-NAME) (0.2 mM), a non-selective inhibitor of NO synthase, failed to completely restore the noradrenaline hyporeactivity of lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed. After L-NAME treatment. Methylene blue (10 microM), a guanylate cyclase inhibitor, produced no additional increase of noradrenaline vasoconstriction in lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed, suggesting that an NO-independent activation of guanylate cyclase may be excluded. In lipopolysaccharide-treated preparations, L-Arg (0.2 mM) elicited a significant increase in nitrite production, which was antagonized by L-NAME. In conclusion, lipopolysaccharide-induced noradrenaline hyporesponsiveness of rat resistance vessels can only be partially explained by NO overproduction. Other mechanisms, probably related to vasoconstriction, may be involved.

Animals↗
PubMed1996

Successful eradicating treatment of Helicobacter pylori in patients with chronic gastritis: gastric levels of cytokines, epidermal growth factor and polyamines before and after therapy.

In 10 patients with Helicobacter pylori (HP) positive chronic gastritis, gastric mucosal content of interleukin (IL)-1 beta, IL-8, Transforming Growth Factor (TGF)-beta 1, Epidermal Growth Factor (EGF) and Polyamines (putrescine, spermine and spermidine) was evaluated before and after eradicating treatment. Histologically, in all patients eradication of HP was accompanied by a marked reduction of the inflammatory infiltrate. At the same time, at the end of the therapeutical regimen, elevated levels of IL-1 beta, IL-8, TGF-beta 1, putrescine and spermidine/spermine ratio significantly dropped, while EGF mucosal content, significantly increased. Results are discussed in terms of the reciprocal role of inflammatory cytokines, growth factors and polyamines in the evolution of the HP-associated chronic gastritis.

Cytokines↗
PubMed1996

In vitro effects of 3'-azido-3'-deoxythymidine (AZT) on normal human polymorphonuclear cell and monocyte-macrophage functional capacities.

The in vitro effects of 3'-azido-3'-deoxythymidine (AZT) (at concentrations of 1, 10 and 100 microM, respectively) on normal human polymorphonuclear cell (PMN) and monocyte-macrophage functional capacities were evaluated. Results show that AZT was able to decrease monocyte phagocytosis only, while PMN polarization, phagocytosis and killing were unaffected by drug pretreatment. Quite interestingly, monocyte-derived macrophages maintained their unaltered phagocytic function in spite of the presence of AZT in overnight cultures, thus indicating that monocytes are more susceptible than macrophages to the antiproliferative effects of AZT. Since our data indicate that AZT affects normal human monocyte phagocytosis, it is advisable to evaluate this immune parameter in HIV+ patients administered with this drug.

Adult↗
PubMed1996

Beta-adrenoceptor responsiveness of splenic macrophages in normotensive and hypertensive rats.

The aim of the present study was to investigate putative mechanisms implicated in the impaired phagocytic response of spontaneously hypertensive rats (SHR)1. The effect of in vitro treatment with isoproterenol (ISO), a beta-adrenergic drug, on phagocytosis and respiratory burst by splenic macrophages (SpMø) from normotensive Wistar-Kyoto rats (WKY) and SHR with established hypertension, respectively, was evaluated. Furthermore, the relaxant effect of ISO was determined in phenilephrine-precontracted thoracic aorta strips from SHR compared with age-matched WKY rats. Results indicate that exposure of rat SpMø to ISO generate a significant and dose-dependent reduction of phagocytosis and oxidative burst which was antagonized, almost completely, by the beta-adrenergic antagonist propranolol (PRO). Unlike normotensive, in hypertensive rats treatment with ISO fail to modulate phagocytosis and respiratory burst activity by SpMø. At vascular level, aortic relaxation by ISO was reduced in SHR when compared to WKY rats. These findings suggest that SHR exhibit changes not only in vascular, but also in macrophage beta-adrenoceptor-mediated responses. It is postulable that sympathetic overactivity could be responsible for impaired phagocytic functions and beta-receptor alterations observed in SHR.

Animals↗
PubMed1996

Immunological effects following administration of interferon-alpha in patients with chronic hepatitis C virus (cHCV) infection.

The immunological effects of interferon (IFN)-alpha administration were evaluated in 15 patients with cHCV infection. Individuals were treated with 6 MU of lymphoblastoid IFN-alpha three times a week for 6 months and with 3 MU three times a week for an additional 6 months. Patients were divided into responders (12 subjects) and nonresponders (3 subjects), respectively, according to alanine aminotransferase serum levels at the end of treatment. Before therapy (T0), absolute numbers of CD3+, CD4+, CD8+, CD14+ and CD16+ cells were significantly reduced in both groups when compared to normal values. At the same time, all patients displayed a profound decrease of phagocytosis and killing exerted by both polymorphonuclear cells (PMN) and monocytes (MO). However, MO Killing resulted to be normal in the responder group. With special reference to T cell function, T cell mediated antibacterial activity, using Salmonella typhi as a target, was also significantly reduced. After therapy (T12), in responder patients a significant increase of CD3+, CD4+, CD14+ and CD16+ cell absolute numbers was observed, while phagocytic and T cell functions were still depressed. Among the nonresponders, in two of three patients IFN-alpha administration gave rise to an increase (above normality) of CD3+, CD4+, CD8+, CD14+, CD16+ and CD20+ cell absolute numbers, while in one patient the same markers dramatically dropped below normal range. In two patients, antibacterial activity was significantly augmented by IFN-alpha treatment, whereas in one patient no modification was observed. Finally, in the same patients IFN-alpha did not correct PMN and MO pretreatment deficits.

Adult↗
PubMed1996

Effects of interferon-alpha treatment on neutrophil oxidative metabolism, lymphocyte proliferation and monocyte HLA class I antigen expression in patients with chronic hepatitis C.

Polymorphonuclear cell (PMN) oxidative metabolism, lymphocyte polyclonal proliferation and monocyte HLA class I antigen expression were evaluated at different intervals of time in patients with chronic hepatitis C (CH-C) subjected to a 6 month interferon alpha (IFN-alpha) treatment and divided into Responder ('R') and Nonresponder ('NR') subsets according to clinical outcome. Before therapy, all subjects exhibited multiple immune alterations even if to a different extent between 'R' and 'NR' subsets: an elevated superoxide anion (O2-) generation by suspended PMN, a failure to further increase neutrophil oxidative responsiveness under adherence conditions, an augmented phytohaemagglutin-induced lymphocyte proliferative capacity and an enhanced HLA class I antigen expression on CD14+ cells. IFN-alpha administration gave rise to a modulation of oxidative response in 'R' group only, since these individuals displayed an O2- release by suspended and adherent PMN which fell within normal values. At the same time, a decrease of lymphocyte proliferation occurred in both groups of patients during IFN-alpha therapy, even if it reached statistical significance in 'R' group only. Finally, a more marked difference between 'R' and 'NR' individuals was noted in terms of HLA class I antigen induction on CD14+ cells at the end of therapy, as a consequence of a reduced expression of these structures in 'NR' subjects. Altogether, these findings suggest the occurrence of a strict relationship between immunoresponsiveness and IFN-alpha induced therapeutical effects in CH-C patients.

Adult↗
PubMed1996

Lipopolysaccharide-, granulocyte-monocyte colony stimulating factor and pentoxifylline-mediated effects on formyl-methionyl-leucine-phenylalanine-stimulated neutrophil respiratory burst in the elderly.

The impairment of superoxide anion (O2-) generation by aged polymorphonuclear cells (PMN) stimulated with formyl-methionyl-leucine-phenylalanine (FMLP) has been reported. In this work the effect of lipopolysaccharide (LPS), granulocyte-macrophage colony stimulating factor (GM-CSF) and pentoxifylline (POF) pretreatment on FMLP-triggered neutrophil oxidative metabolism in a group of healthy elderly individuals, was investigated. Results provide evidence that LPS and/or GM-CSF priming was able to enhance O2- production in old PMN, even if values were still lower than those observed in similarly-treated young cells. Moreover, even if the lag period was unaffected by inflammatory mediator treatment, the priming gave rise to a significant increase of maximum O2- release rate. On the contrary, POF pretreatment led to a significant decrease of oxidative responsiveness in either unprimed or primed PMN suspensions. These findings suggest the occurrence of different mechanisms in the imbalance of FMLP-activated neutrophil oxidative responsiveness during senescence. This may be of paramount significance for explaining the augmented frequency of severe infectious diseases with advancing age.

Aged↗
PubMed1996

Hepatitis C virus infection. Biological and immunological features.

The recent cloning and genomic identification of hepatitis C virus (HCV) by sensitive and specific immune techniques has allowed a better definition of both histopathological and clinical features of the previously not well defined non-A, non-B hepatitis. In this regard, antibodies to different HCV antigens are usually found during infection, even if some of them such as anti-E1 and anti-E2/NS1 have been shown to be associated with significant viraemic levels. Acute hepatitis C is self-limiting in a minority of cases only. Over 60% of acute hepatitis becomes in fact chronic and may progress towards cirrhosis. In about 10% of cases, hepatocellular carcinoma may develop in cirrhotic livers. The occurrence of a strict relationship between immunoresponsiveness and disease activity is suggested by the observation that peripheral blood mononuclear cell (PBMC) proliferation induced by NS3 structure is associated with self-limiting acute hepatitis, while PBMC stimulation by core antigen characterizes chronic C hepatitis. The demonstration of lymphoid aggregates, bile duct lesions, intraportal lymphocyte infiltration, increased adhesion molecule expression and augmented cytokine release clearly emphasizes the involvement of immune-mediated reactions in the development of liver damage, even if a direct cytopathic effect cannot be excluded. Finally, it is likely that HCV may favour, through immune-mediated mechanisms, autoantibody generation and/or the appearance of some extrahepatic autoimmune manifestations during the course of HCV chronic infection.

Animals↗
PubMed1996

Neutrophil activation in nickel sensitized subjects.

Conflicting results were obtained from the evaluation of nickel-mediated effects on immunoresponsiveness. A reduction of B cell polyclonal response, mixed lymphocyte reaction, T lymphocyte proliferation and natural killer cytotoxicity was evident following nickel salt exposure. On the contrary, an enhancement of cytokine release, T cell proliferative capacity and adhesion molecule expression was found in nickel sensitized donors. In addition, under different experimental conditions, respiratory burst induction and myeloperoxidase release by polymorphonuclear cells (PMN) in a group of individuals exhibiting nickel hypersensitivity were investigated. Results provide evidence that nickel allergic individuals displayed a significant increase of superoxide anion (O2-) generation by suspended PMN in comparison with similar cell suspensions from healthy donors, but this was not the case when adherent neutrophils were used as effector cells. PMN from nickel sensitized donors exhibited a significant enhancement of hydrogen peroxide (H2O2) and myeloperoxidase release. The results imply the occurrence of neutrophil activation in nickel hypersensitivity, which in turn may be responsible for the low frequency of life-threatening infections in these subjects.

Adult↗
PubMed1995

Parasite escape mechanisms: the role of Leishmania lipophosphoglycan on the human phagocyte functions. A review.

Protozoan parasites of the Leishmania genus are the causative agents of important diseases in humans and animals. During their life cycle in vertebrate hosts, protozoa are able to live and proliferate within phagolysosomes of host phagocytic cells. The capacity to live in this hostile environment is likely due to the cell surface glycoconjugate expression. In particular, lipophosphoglycan (LPG), a major surface glycoconjugate of Leishmania promastigotes, has been reported to play an active role in protecting parasites within phagolysosomes via the impairment of killing mechanisms. In this review, the authors emphasize some novel LPG-mediated escape mechanisms of promastigotes from human phagocyte responses, such as the impairment of oxidative burst and of chemotactic activity. In the light of these findings, the knowledge of biological actions of LPG may be useful in order to prepare a vaccine against human leishmaniasis, using LPG defective avirulent mutant strains.

Animals↗
PubMed1995

Evaluation of cellular immune responses and soluble mediators in patients with chronic hepatitis C virus (cHCV) infection.

In 54 patients with cHCV infection, peripheral immune responsiveness and soluble mediator release were evaluated. Results demonstrate that in these patients phagocytosis and killing capacities exerted by polymorphonuclear cells and monocytes were profoundly depressed. At the same time, absolute numbers of CD3+, CD8+ and CD16+ cells were reduced, while the CD4(+)-CD8+ dependent antibacterial activity was also impaired. With special reference to soluble mediators, elevated amounts of both soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 were detected in sera of patients. By contrast, serum levels of tumor necrosis factor-alpha were within normal ranges, whereas interferon-gamma serum concentrations were decreased. Of note, in 18.5% of cHCV patients circulating levels of bacterial lipopolysaccharides (LPS) were detected by means of Limulus assay. In the Limulus+subset of patients, absolute numbers of CD14+ cells were reduced in a significant manner, this implying a putative monocyte-LPS interaction. In conclusion, the overall results indicate a condition of peripheral immune depression in cHCV patients with an exaggerated shedding of various mediators endowed with noxious effects for the host.

Adult↗
PubMed1995

Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact: a possible role for membrane-associated interleukin-6 and interleukin-8.

Polymorphs (PMN) and monocytes/macrophages (Mo) play a very important role in the host defence since they participate to inflammatory processes, tissue repairing and antitumor activity. Previous studies showed that lipopolysaccharide (LPS)-activated Mo are able to upregulate PMN phagocytic ability via cell-to-cell contact mechanisms mediated by bound to Mo membrane (m) cytokines (CKs), such as Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-1 alpha and IL-1 beta. Based on these grounds, the role of Mo m-associated IL-6 and IL-8 on the modulation of PMN activity has been evaluated. In the first step, PMN incubated with lipid A (LA)-activated Mo showed an increased phagocytosis dependent on cell-to-cell contact only. In the second step, LA-activated Mo were pretreated with antirecombinant human (Rhu) IL-6 and IL-8 monoclonal antibodies (MoAbs), respectively and, in such a way, the enhanced phagocytic activity of PMN was abrogated. In the third step, PMN incubated with LA-activated supernatants (AS) from PBMC cultures exhibited an enhanced phagocytic activity, that was abrogated when LA-AS were pretreated with anti-Rhu IL-6 and anti-Rhu IL-8 MoAbs, respectively. These data suggest that IL-6 and IL-8 associated to Mo membrane may modulate PMN activation through a cell-to-cell contact dependent pathway.

Adult↗
PubMed1995

Role of lymphocyte function-associated antigen-1 on the interplay between lipid A-activated monocytes and polymorphonuclear cells.

Previous findings provided evidence that bacterial lipopolysaccharide (LPS)-activated human monocytes are able to upregulate autologous polymorphonuclear (PMN) phagocytic ability via cell-to-cell contact mechanisms mediated by membrane (m)-associated cytokines (CKs), such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6 and IL-8. Consequently, the role of the lymphocyte function-associated antigen (LFA)-1 molecule on the monocyte (Mo)-PMN interplay was evaluated. In the first step, lipid A (LA)-stimulated Mo were pretreated with anti-recombinant human (Rhu) LFA-1 alpha monoclonal antibody (MoAb), and the enhanced phagocytic activity of PMN was abrogated. Pretreatment of unstimulated Mo with the same MoAb led to a reduction of PMN phagocytosis. In the second step, the role of m-LFA-1 on PMN was investigated with regard to Mo modulation. Anti-Rhu LFA-1 alpha MoAb was supplemented to LA-activated and unstimulated PMN, respectively, before coculturing with autologous LA-activated Mo. The addition of anti-Rhu LFA-1 alpha MoAb gave rise to a significant decrease in PMN phagocytosis regardless of PMN activation. These data suggest that, besides m-CKs, LFA-1 present on Mo and PMN might be involved in the mutual interplay between PMN and Mo.

Antibodies, Monoclonal↗