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Biomedical subjects

E Jirillo

Publications and source records attributed to E Jirillo.

At least 91 records · Page 5Linked to original sources

Impairment of the human phagocyte oxidative responses caused by Leishmania lipophosphoglycan (LPG): in vitro studies.

Lipophosphoglycan (LPG), a surface glycoconjugate of Leishmania promastigotes, has been reported as playing an active role in protecting the parasite within phagolysosomes, by an impairment of monocyte oxidative responses. In this study the effect of LPG on the oxidative burst of human peripheral monocytes, eosinophils and neutrophils was evaluated. Our results demonstrated that either superoxide anion (O2-) or hydrogen peroxide (H2O2) release by LPG-pretreated cells was diminished, emphasizing the ability of this glycoconjugate to impair the oxidative activity of all phagocytes.

Animals↗

Could migraine be a "protective factor" against tumors?

Patients with migraine headaches show significantly lower prevalence of malignant neoplasms when compared with the general control group or the age-matched control group. Conversely, no significant difference concerning the family history for neoplasms has been found between the two groups. Nevertheless, headache and cancer in a family member in migraneous are not coexistent. Although more extensive, epidemiological studies are necessary to confirm our data, it is suggested that some particular biochemical or psychologic aspects involved in the pathogenesis of migraine might represent the presence of a protective factor against neoplasm development.

Adolescent↗

Decrease of phagocytic functions in hypertensive rats.

The present investigation was aimed to examine non-specific immunologic capabilities of spontaneously hypertensive rats (SHR) during the development of hypertension. In vitro phagocytosis and oxidative killing exerted by monocytes, polymorphonuclear cells (PMN) and splenic macrophages (SpM0) were evaluated in SHR at 5-, 8-, and 24-weeks of age. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Results showed that in pre-hypertensive stage (5-wk) there was no difference between SHR and WKY rats with regard to non-specific immunologic functions. Statistically significant differences in both phagocytosis and oxidative killing arose in early hypertensive stage (8-wk) and became more marked in adult SHR with established hypertension (24-wk). In conclusion, our data provide evidence of novel immunologic abnormalities in SHR in terms of ingestion and bactericidal phagocytic capabilities. The mechanisms responsible for these impaired immunologic functions may depend on various suppressive factors which will be object of discussion.

Aging↗

Changes in the frequency of splenic immunocompetent cells in rats exposed to carbon monoxide during gestation.

The aim of the present study was to evaluate whether prenatal exposure to relatively low concentrations of carbon monoxide (CO) may alter the frequency of splenic cells either in young (15-21 days) or in aged rats (18 months). Wistar female rats were exposed to 75 and 150 ppm of CO from day 0 to day 20 of pregnancy, respectively. The results show that prenatal exposure to 150 ppm of CO significantly decreases the number of leucocyte common antigen (LCA+) cells in 21 day old male rats, whereas other cellular populations, such as macrophages, Major Histocompatibility (MHC) II cells, T and B lymphocytes display only a trend towards a reduction without achieving statistical significance. The alterations in LCA+ cell frequency produced by gestational exposure to CO were reversible. These data further extend previous findings showing that rats prenatally exposed to moderate concentrations of CO exhibit subtle immunological changes in the absence of overt signs of toxicity.

Aging↗

Downregulation of human polymorphonuclear cell activities exerted by microorganisms belonging to the alpha-2 subgroup of Proteobacteria (Afipia felis and Rochalimaea henselae).

Intracellular pathogens have evolved effective mechanisms in order to survive in an intracellular environment, thus avoiding destruction by phagocytic cells. In this regard, a correlation between resistance to phagocytic killing and expression of pathogenic potency has been established. In this report, we have studied the interaction between human polymorphonuclear cells (PMN) and two gram-negative microorganisms, Afipia felis and Rochalimaea henselae, which belong to the alpha-2 subgroup of the class Proteobacteria. A. falis has been previously proposed as the causative agent of Cat Scratch Disease (CSD), but several recent lines of evidence attribute a major role to R. henselae. Of note, CSD is a syndrome characterized by a chronic lymphoadenopathy, involving macrophages and endothelial cells with a progression towards a granulomatous process and/or angiogenesis. Since members of the alpha-2 subgroup of Proteobacteria have the property to survive intracellularly, we have evaluated the effects exerted by A. felis and R. henselae on human PMN in terms of chemotaxis locomotion, degranulation and oxidative metabolism. Results will show an impairment of PMN activities as a consequence of the challenge with both microrganisms. In particular, inhibition of PMN oxidative function occurred either as result of a direct exposure to both A. felis and R. henselae or when PMN were primed by bacteria for the N-formyl-methionyl-leucyl-phenylalanine enhancement of the oxidative burst. These findings may account for the ability of A. felis and R. henselae to survive within PMN as expression of a further mechanism of pathogenic potency, influencing also the nature and the evolution of inflammatory response in the lesion sites.

Bartonella henselae↗

Age-associated changes of neutrophil responsiveness in a human healthy elderly population.

Conflicting results have been reported on polymorphonuclear (PMN) cell responsiveness during senescence. Consequently, neutrophil absolute numbers and PMN-mediated chemotaxis, phagocytosis, killing and superoxide anion (O2-) generation in healthy aged volunteers divided into different groups according to increasing age criteria, were investigated and evaluated. Data provide evidence that absolute amounts of PMN cells declined in a significant manner in donors over 85 years old only when compared with young subjects. On the contrary, regardless of age, the aged individuals exhibited a significant impairment of PMN chemotactic, phagocytic and killing functional capacities. Finally, formyl-methionyl-leucyl-phenylanaline (FMLP)-triggered O2- release was reduced in all elderly groups, while depression of O2- production was seen in subjects between the age of 86 and 104 years using phorbol 12-myristate 13-acetate (PMA) as agonist. These findings indicate that an imbalance in the PMN cell immune reactivity occurs throughout the senescence process.

Adult↗

Modulation of pokeweed mitogen-induced B cell differentiation by polymorphonuclear cells: effects of bacterial lipopolysaccharides.

The capacity of polymorphonuclear (PMN) cells to release several cytokines stresses the potential immunomodulatory role of these cells. The effects mediated by purified PMN cell suspensions on pokeweed mitogen (PWM)-driven B cell differentiation was investigated. Results showed that the addition of increasing concentrations of resting PMN cells to peripheral blood mononuclear cell (PBMC) cultures gave rise to inhibition of immunoglobulin (Ig) production. At the same time, similar results were obtained using lipopolysaccharide (LPS)-pretreated PMN cells. In contrast, when LPS, at different concentrations, and PMN cells were both added to PBMC cultures an enhancement of IgG or IgM release in comparison with cultures treated with PMN cells only occurred at low PMN cell/PBMC ratios (1:20 and 1:10), which was maximal in the presence of 10 or 100 ng/ml LPS. This effect was probably mediated by LPS-induced monocyte stimulation, since the supplementation of LPS-activated monocyte supernatants to PMN cell/PBMC cocultures led to an Ig synthesis which mimicked that seen in similarly-treated PBMC cultures. These data suggest the occurrence of various in vitro modulatory effects in the interactions between PMN, LPS and lymphocytes in a PWM-induced B cell polyclonal responsiveness system.

B-Lymphocytes↗

Rochalimaea henselae organisms possess an elevated capacity of binding to peripheral blood lymphocytes from patients with cat scratch disease.

Cat scratch disease (CSD) is a clinical condition whose aetiological agent, according to recent findings, is of bacterial origin. Two Gram-negative bacteria are invoked as causative agents of CSD, namely Afipia felis and Rochalimaea henselae. In this paper, five patients with suspected CSD were studied in terms of binding capacity of A. felis and R. henselae to their own peripheral blood lymphocytes (PBL). This parameter was correlated with serum antibody titres to both A. felis and R. henselae, as determined by an indirect fluorescence assay (IFA). Results demonstrate that in four out of five cases binding of R. henselae to PBL was higher than that observed with A. felis. In two cases serum antibody titres to both bacteria were lower or absent, while in the other two patients serum antibody titres to R. henselae were significantly high. In one case only, characterized by elevated titres of serum antibodies to A. felis, values of cytoadherence exhibited by this bacterium were similar to those observed with R. henselae. The results suggest that bacterial binding to lymphocytes may represent an additional parameter to support diagnosis of CSD.

Adolescent↗

Studies on the epidemiology of child infections in the Bari area (south Italy). VII. Epidemiology of Epstein-Barr virus infections.

Serological patterns against Epstein-Barr virus (EBV) specific antigens were determined in 3732 healthy babies and children aged 0-10 years living in the Bari area (South Italy). IgG antibodies against EBV capsid antigen (VCA) were found in 2713 subjects (72.7%). Seropositivity rates, high in the first semester of life (83.8%), declined between 6 and 12 months (65.6%) and even further between 1 and 2 years (43.8%). After 2 years the frequency of positive children rose progressively reaching steady levels between 5 and 7 years (80.2%) and between 8 and 10 years (81.9%). IgA antibodies against VCA, IgG anti-early viral antigen (EA) and IgG against virus-associated nuclear antigens (EBNA) were found in 17.9%, 15.9% and 25.7% of the subjects tested, respectively. IgM anti-VCA were found only in 35 (0.9%) children, but 818 (21.9%) exhibited antibody patterns suggestive of a recent infection: IgG anti-VCA > or = 1:160 alone or in association with IgA anti-VCA or IgG anti-EA or both. These results suggest that in this area the primary infection by EBV occur early in life, with immunity to EBV acquired primarily after 4 years.

Antibodies, Viral↗

Relationship between respiratory burst and adhesiveness capacity in elderly polymorphonuclear cells.

Polymorphonuclear cell (PMN) activation was assessed in 30 aged donors, in terms of either adherence to different substrates or superoxide anion (O2-) generation by adhering and suspended cells in response to several agonists. Results showed that PMN in suspension from elderly individuals displayed a phorbol 12-myristate 13-acetate (PMA)-triggered O2- responsiveness which overlapped that seen in the younger counterpart, while a significant decrease of respiratory burst was observed in the presence of formyl-methionyl-leucine-phenylalanine (FMLP). Moreover, in spite of a normal nylon fiber adhesiveness, aged individuals exhibited a reduced PMN adherence to foetal calf serum (FCS)-coated plastic surfaces by using either PMA or FMLP as stimulant. However, elderly adhering cells produced higher amounts of O2- than homologous neutrophils in suspension. Cell pretreatment with anti-CD11b, anti-CD11c and anti-CD18 antibodies led to a further inhibition of PMN adhesion to FCS-coated plates. By contrast, under the same experimental conditions, O2- generation from adhering cells was reduced by using anti-CD18 antibody only. Altogether, these findings provide additional evidence for an imbalance of PMN-mediated functions in the elderly.

Adult↗

Immunological changes produced in rats by prenatal exposure to carbon monoxide.

Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (CO) (75 and 150 p.p.m.) from day 0 to day 20 of pregnancy. The results show that splenic macrophage phagocytosis of Candida albicans was significantly decreased in 15 and 21 day old male rats exposed to CO (150 p.p.m.) during pregnancy. Moreover, splenic macrophage killing was significantly reduced in 15 day old male pups prenatally exposed to 75 and 150 ppm of CO. Prenatal CO (150 p.p.m.) significantly decreased splenic macrophage O2- release in both 15 and 21 day old pups. CO-induced alterations in the immune system were not observed in 60 day old rats. These findings indicate that gestational exposure to relatively mild concentrations of CO induces in rat offspring reversible immunological changes characterized by an altered splenic macrophage function.

Animals↗

In vivo effects of alprazolam and lorazepam on the immune response in patients with migraine without aura.

Over the past few years, the immunomodulating role of benzodiazepines (BDZ) has been reported in literature. In particular, diazepam is an inhibitory BDZ with regard to its effects on the phagocytic and metabolic activities of polymorphonuclear cells (PMN) and monocytes, while triazolobenzodiazepines (alprazolam and triazolam) upregulate normal human peripheral blood T lymphocyte function. On these grounds, the administration of alprazolam (1 mg/per day for 1 month) in 13 patients with migraine without aura (MWA) and of lorazepam (2 mg/per day for 1 month) in 10 matched MWA subjects has been evaluated in terms of immune response. Results show that before administration of BDZ in both groups of patients phagocytosis and killing of PMN and monocytes were profoundly depressed and the same was true for the lymphocyte-dependent antibacterial activity. After one month treatment lorazepam further decreased lymphocyte function without modifying phagocytic capabilities. On the contrary, alprazolam increased PMN phagocytosis and killing and monocyte phagocytosis without modifying antibacterial activity values. Taken together, these results further support the existence of different classes of BDZ in terms of their immunomodulating capacities. Moreover, alprazolam seems to be a more appropriate BDZ for treating immunocompromised patients, even including MWA patients.

Adolescent↗

Effectiveness of thymostimulin and study of lymphocyte-dependent antibacterial activity in children with recurrent respiratory infections.

Recurrent respiratory infections (RRI) consist of more relapsing acute respiratory infections than the ones expected for the age [> 6 acute respiratory tract infections (RTI) per year if age is > 3 years, and > 8 acute RTI per year if age is < 3 years]. Concerning the pathogenesis of RRI, several investigations report the important role of environmental factors, early socialization and immunological dysfunctions, such as lymphocyte subpopulations alterations, IgG subclass deficiency and phagocytosis and/or opsonization deficit during acute infections. In this framework, we have studied the lymphocyte-dependent antibacterial activity (ABA) among 121 children affected by RRI. Results show a statistically significant alteration of this function in 38 children (31.4%): 19 of them exhibited an absent ABA (group 1), while in the others same function was reduced (group 2). A bovine thymic extract, thymostimulin, was administered to both groups by intramuscular injections (1 mg/kg) for a 3 month cycle. At the end of therapy we observed a statistical significant rise of ABA only in group 1 and among children aged > 3 years. Among the same patients, 33 children (86.8%) improved in terms of reduction of clinical score and better results were seen among children aged > 3 years. These data emphasize the beneficial role of thymostimulin in RRI-affected children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factor.

Adjuvants, Immunologic↗

Supplementation of male inhibitory material to lipid A activated human mononuclear cell supernatants contributes to the suppression of polymorphonuclear cell phagocytosis.

Human normal peripheral blood mononuclear cells were stimulated with lipid A (LA), the biologically active moiety of bacterial lipopolysaccharides. LA-activated supernatants were able to suppress polymorphonuclear cell (PMN) phagocytosis of Candida albicans. This inhibitory activity was enhanced by the supplementation of male inhibitory material (MIM) to active supernatants. The addition of a recombinant human anti-interleukin-1 beta monoclonal antibody to activated supernatants in the absence or presence of MIM diminished or abrogated, respectively, the suppressive effect on PMN function. The mechanisms and the significance of MIM-mediated inhibition of phagocytosis under these circumstances are discussed.

Adult↗

Cerebrospinal fluid myelin basic protein as predictive marker of demyelination in AIDS dementia complex.

Myelin basic protein (MBP) was measured in cerebrospinal fluid (CSF) of patients with acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) in order to investigate the degree of white matter destruction. Results show that increased CSF levels of MBP were detected in all patients with severe ADC (10/10) and, less often, in subjects with mild (2/7) or moderate dementia (7/16). No evidence of MBP-elevated concentration was observed in 14 human immunodeficiency virus (HIV)-seropositive subjects without neurological disorders and in nine HIV-seronegative controls. Our findings suggest that the measurement of CSF MBP concentration may represent a predictive marker of myelin injury and neurologic damage during the course of ADC.

AIDS Dementia Complex↗

L-carnitine deficiency in AIDS patients.

OBJECTIVE: To evaluate carnitine (3-hydroxy-4-N-trimethyl-ammoniobutanoate) deficiency in AIDS patients by measuring serum total, free and short-chain carnitine concentrations. DESIGN: We conducted an open study. SETTING: All patients were seen at the Infectious Diseases Clinic, Università 'La Sapienza', Rome, Italy. PATIENTS, PARTICIPANTS: Twenty-nine AIDS patients, aged 27-41 years, with a previous history of drug use; and 14 healthy age- and sex-matched controls were studied. INTERVENTIONS: Study subjects were administered 500-800 mg zidovudine daily for 2 to 28 months (8 +/- 6 months). MAIN OUTCOME MEASURES: Carnitine deficiency was suspected in study participants prior to data collection because of previously reported cardiac symptoms, muscle weakness, hypometabolism and/or cachexia. RESULTS: A marked decrease in total and free carnitine was observed in 21 (72%) subjects. Nine of these patients also had low levels of short-chain carnitine. CONCLUSIONS: AIDS patients may become carnitine-depleted and therefore at risk for alterations in fatty-acid oxidation and energy supply.

Acquired Immunodeficiency Syndrome↗

Tumour necrosis factor (TNF-alpha) and neurological disorders in HIV infection.

Tumour necrosis factor (TNF-alpha) concentrations were determined in the CSF from 42 HIV-infected patients, with or without CNS involvement. In addition, 14 subjects with various neurological disorders but without HIV antibodies were included as controls. Raised CSF concentrations of TNF-alpha (greater than 40 ng/l) were detected both in patients with AIDS dementia complex (ADC) (6/9) and with CNS opportunistic infections (10/19) and, less commonly, in HIV infected subjects without CNS diseases (2/14) and in anti-HIV negative controls (1/14). The highest CSF concentrations of TNF-alpha (greater than 100 ng/l), however, were found in seven out of eight patients with cryptococcal meningitis. Although a role for TNF-alpha in demyelinating lesions associated with ADC has been suggested, our results indicate that a clear elevation of TNF-alpha in the CSF from HIV positive patients mostly occurs in acute inflammatory disorders, such as cryptococcal meningitis.

AIDS Dementia Complex↗

Interleukin-1 beta and beta-endorphin circadian rhythms are inversely related in normal and stress-altered sleep.

Normal sleep is associated to physiological nocturnal rises in Interleukin 1 beta (IL 1 beta) secretion. The 24 h pattern of IL 1 beta, beta-Endorphin (beta-EPH), ACTH and cortisol (F) production was evaluated in four male healthy volunteers. Two subjects were unable to sleep, due to the stress of the experiment; in these cases, no detectable plasma IL 1 beta secretion, both diurnal and nocturnal, was present, beta-EPH plasma levels were significantly higher (p < 0.01) than in the subjects who slept regularly and, in one case, increased F plasma levels were also reported. A strong negative correlation between IL 1 beta and beta-EPH plasma levels was present in all the cases. In conclusion, stress-induced sleep alterations might deeply affect both diurnal and nocturnal IL 1 beta plasma secretion, probably due to the hypothalamus-pituitary-adrenal axis (HPAA) activation, and beta-EPH might be the reliable marker of the stress-induced HPAA activation level.

Adrenocorticotropic Hormone↗