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Biomedical subjects

E Jirillo

Publications and source records attributed to E Jirillo.

At least 109 records · Page 6Linked to original sources

Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact. A possible role for membrane-associated cytokines.

Previous findings have shown that lipopolysaccharide (LPS)-activated human monocytes express cytokines (CKs) on their membrane. Furthermore, those associated to membrane products such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been demonstrated to exert many biological activities. In this paper, evidence is provided that human polymorphonuclear cells (PMN) exhibited an increased phagocytic capacity following incubation with either lipid A (LA)-activated autologous monocytes or supernatants recovered from LA-stimulated mononuclear cell cultures. In order to investigate the possible role of monocyte membrane-associated TNF-alpha, IL-1 alpha and IL-1 beta in the modulation of PMN activity, in a separate series of experiments LA-activated monocytes or LA-activated supernatants were pretreated with anti-recombinant human (Rhu) TNF alpha, anti-Rhu IL-1 alpha and anti-Rhu IL-1 beta monoclonal antibodies (MoAbs), respectively. Such an approach gave rise to an abrogation of monocyte-mediated triggering effect on PMN functional capacity. Taken together, these data suggest that activated monocytes can upregulate PMN phagocytosis by a cell-to-cell contact mechanism, likely related to membrane-associated CKs.

Antibodies, Monoclonal↗

Thymostimulin administration modulates polymorph metabolic pathway in patients with chronic obstructive pulmonary disease.

Several studies outline the imbalance of phagocyte functions in chronic obstructive pulmonary disease (COPD). In this regard, here, we have assessed either monocyte- and polymorphonuclear cell (PMN)-mediated chemotactic, phagocytic and killing capacities or PMN-triggered metabolic pathway in a group of COPD patients before and at different times after thymostimulin administration. Before therapy, an increase of O2-generation and a decrease of myeloperoxidase release were found in these individuals when compared to controls. Moreover, a reduction of either PMN-mediated chemotaxis and killing or monocyte chemotactic capacities was observed. By contrast, no differences were seen in terms of beta-glucuronidase release, monocyte-mediated killing and PMN or monocyte phagocytic function. During a one-year monitoring following immunotherapy, O2- production and myeloperoxidase activity fell within normal values, while phagocyte functional capacities were unaffected by such a treatment. Furthermore, COPD subjects exhibited a significant improvement of their clinical status as assessed during a one-year followup. All together, these findings suggest a potential role for thymostimulin in the treatment of COPD patients.

Adjuvants, Immunologic↗

Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and peripheral blood B lymphocytes.

In 15 elderly individuals lyophilized Bifidobacterium bifidum (BB) and Lactobacillus acidophilus (LA) (Infloran) were administered in capsules (two capsules 4 times per day) for 28 days, while in 10 elderly controls placebo were given the same posology and for an equal period of time. The effects of this treatment on the immune system both at the periphery or the intestinal level were investigated. Results show that BB and LA significantly reduced the colonic inflammatory infiltration, without altering T, B and Leu7 + cell percentage. At the same time, a significant increase of B cell frequency in the peripheral blood was noted, in comparison to controls. The overall results suggest that the regular administration of BB and LA leads to a modulation of the immunological and inflammatory response in elderly subjects.

Aged↗

On the physiological significance of tumor necrosis factor-alpha in the human amniotic fluid.

Tumor Necrosis Factor (TNF)-alpha and Interleukin (IL)-1 beta levels have been measured in 16 weeks gestation amniotic fluids and mother's sera. Detectable levels of TNF-alpha were found in amniotic fluids, while IL-1 beta was absent. No cytokines were detected in mother's sera. The possible role of TNF-alpha as growth factor for fetal hematopoietic cells is discussed.

Acute-Phase Proteins↗

[Isoproterenol causes changes in the mitochondrial energy metabolism in the rat heart].

In this paper we report observations on kinetic and structural characteristics of mitochondrial ATP synthase of rat-heart after subcutaneous injection of isoproterenol. The results obtained indicate: a decrease of respiratory rate either in absence (state 4) or in presence (state 3) of oxidative phosphorylation; decrease of respiratory control ratio; decrease of ATP hydrolase activity in sonic submitochondrial particles; decrease of relative content of the catalytic subunit F1 with respect to the membrane sector F0. The data obtained are in favour of the hypothesis that isoproterenol causes structural and functional alterations of mitochondrial ATP synthase.

Adenosine Triphosphatases↗

Neurological damage mediated by cytokines.

Our results suggest that CKs, in particular Interleukin-1 and Tumor Necrosis Factor (TNF)-alpha, are involved in the pathogenesis of some neurological disorders and HIV infection. Infact, we observed an exaggerated spontaneous release of TNF-alpha in patients with migraine without aura. Furthermore, in a broad spectrum of patients with HIV-infection we have also found increased amounts of serum TNF-alfa and IL-1. Interestingly, a strict correlation between plasma lipopolysaccharide (LPS) and IL-1 or TNF-alpha levels seems to exist in both group of patients, thus indicating that LPS could account for the production of CKs in the course of the above diseases.

AIDS Dementia Complex↗

Role of interleukin 2, interleukin 4 and interleukin 5 in the T helper cell-driven B cell polyclonal differentiation in the elderly.

There is evidence for an impaired T cell-mediated B cell response during senescence. In thirty aged donors, pokeweed mitogen (PWM)-driven immunoglobulin (Ig) synthesis by B cells co-cultured with autologous enriched CD4+ lymphocytes and low amounts of monocytes, was evaluated. Under such experimental conditions, elderly cultures displayed a reduced IgG and/or IgM production when compared with the younger counterpart. Moreover, interleukin (IL)-2 and/or IL-5 addition to cultures led to an enhancement of Ig release. In contrast, IL-4 supplementation failed to positively modulate B cell differentiation. At the same time, aged cells cultured in the presence of IL-2 + IL-5 exhibited an increased Ig synthesis, while the addition of IL-2 + IL-4 or IL-4 + IL-5 mixtures did not induce any significant effect in comparison with homologous untreated samples. The results suggest a critical role for IL-2, IL-4 and IL-5 in the modulation of T helper cell-driven B cell polyclonal responsiveness in the elderly.

Aged↗

Influence of ST 789 on interleukin-1, interleukin-2 and interferon-gamma production from normal human peripheral blood mononuclear cells.

ST 789, previously named PCF 39, is a synthetic hypoxanthine derivative endowed with immunomodulating properties. However, the mode of action of this compound on immunocompetent cells has not yet been elucidated and, in particular, no evidence has been provided on its ability to trigger monokine (MK) and lymphokine (LK) release. In this framework, here we have evaluated the influence of ST 789 on interleukin (IL)-1, IL-2 and interferon (IFN)-gamma production from normal human peripheral blood mononuclear cells (PBMC). Results will show that following stimulation of PBMC with lipopolysaccharides (LPS) or lectins [phytohemagglutinin (PHA) and concanavalin A (Con A)] in the presence of increasing concentrations of ST 789 no modification of cytokine release is obtained, in comparison with cultures activated with LPS or lectins. In addition, this hypoxanthine is not able per se to induce release of MKs and LKs. The overall results suggest that ST 789 acts on the immune system through mechanisms which are not dependent on the release of ILs and IFN-gamma.

Adjuvants, Immunologic↗

On the spontaneous adherence of myelin basic protein to T lymphocytes.

We have applied a double tagging system in order to study whether purified myelin basic protein is able to adhere to normal human peripheral T lymphocytes without the need to purify cells. Evaluation of myelin basic protein adherence to peripheral blood mononuclear cells was determined with biotinylated myelin basic protein and fluoresceinated avidin, and lymphocyte population was identified by the corresponding phycoerythrinated monoclonal antibody. The observed adherence of myelin basic protein to T lymphocytes was found to depend on protein conformation.

Animals↗

Human melanoma metastasis culture supernatant contains chemotactic factors for phagocytes.

Several findings point out that melanoma culture supernatants release soluble factors which modulate mononuclear cell chemotactic responsiveness. In this regard, either an enhancement or an impairment of chemotactic capacity has been found. Here, we provide evidence that supernatant recovered from human melanoma cell metastasis culture is able to trigger monocyte and polymorphonuclear cell chemotaxis. This activity is not affected by the presence of anti-IL-1 antibody during the assay. Further studies are in progress to isolate and characterize soluble factors involved in this activity.

Chemotactic Factors↗

Detection of cerebrospinal fluid antibodies against myelin basic protein in patients with AIDS dementia complex.

We evaluated cerebrospinal fluid (CSF) antibody levels against a lipid-free, denatured form of myelin basic protein (LF-MBP) in 11 patients with AIDS dementia complex (ADC) by using an enzyme-linked immunosorbent assay (ELISA). In 9 out of 11 patients, anti-LF-MBP antibody levels were significantly higher than those observed both in 15 human immunodeficiency virus (HIV)-infected patients without neurological disorders and in 9 anti-HIV-negative subjects affected by other neurological diseases. Furthermore, we followed up anti-MBP levels in 5 out of the 11 ADC patients and detected a strict relationship with the encephalopathy progression. At the same time, with the aim to detect early demyelinating events we investigated CSF antibody levels against a lipid-bound, native-like form of MBP (LB-MBP). Results did not show any significant difference between LF-MBP and LB-MBP in terms of antibody reactivity. The detection of anti-MBP antibodies in CSF may provide the opportunity to assess a diagnostic tool for discovering demyelinating lesions in ADC patients.

AIDS Dementia Complex↗

Inosine pranobex in the treatment of HIV infection: a review.

Inosine pranobex (InPx) could prove a valuable and innovative approach to the treatment of HIV-infected patients, since InPx administration has been shown in two multicenter trials to effectively delay the progression of HIV infection to overt AIDS. However, further studies are strongly required to optimize both the dosage of inosine pranobex and the administration schedules. Furthermore, clinical trials evaluating combination therapy of HIV infection with both InPx and zidovudine should ultimately provide an important advance in the management of HIV-infected patients. Our finding that concomitantly administered InPx to zidovudine-receiving patients increased the plasma levels of zidovudine as well as prolonged zidovudine mean half-life during InPx treatment suggests several potential advantages of the combination treatment with both InPx and zidovudine, such as a need for lower zidovudine dosage and a longer interval period between administering zidovudine to obtain sustained plasma levels as well as a potential to enhance residue immune function resulting from inosine pranobex treatment.

Drug Therapy, Combination↗

Increased spontaneous release of tumor necrosis factor-alpha/cachectin in headache patients. A possible correlation with plasma endotoxin and hypothalamic-pituitary-adrenal axis.

Tumor Necrosis Factor-alpha/cachectin (TNF-alpha/cachectin), Lipopolysaccharide (LPS), ACTH, beta-Endorphin (beta-EPH), and Cortisol (F) levels were determined in 33 Headache patients: 22 patients were affected with Migraine (M) and 11 patients with Chronic Type Tension Headache (CTTH). TNF-alpha/cachectin serum level was detected in 15 out of 22 migraneous patients and in no CTTH patients. Plasma LPS was observed in 11 out of 15 TNF-alpha/cachectin positive migraneous patients (73%) and in 3 out of 11 CTTH patients (27%). A negative correlation was observed between TNF-alpha/cachectin values and either ACTH or beta-EPH. In the group of migraneous patients the presence of serum TNF-alpha/cachectin showed a sensibility of .6 and a specificity of 1. The endocrine and immunological implications concerning these data are discussed.

Adrenocorticotropic Hormone↗

Modulating effects on CD25 and CD71 antigen expression by lectin-stimulated T lymphocytes in the elderly.

During the last few years, several observations outline that the impaired T lymphocyte proliferative capacity in the elderly is due to a reduced interleukin 2 (IL-2) release. To further investigate the activation process during lectin stimulation, aged peripheral blood mononuclear cells (PBMC) were stimulated with phytohemagglutinin (PHA) and assessed for CD25 (IL-2 receptor) and CD71 (transferrin receptor) expression at different intervals of time. Our results provided evidence for a significant decline of both structure induction, above all in the later phase of culture. Indomethacin (INDO) treatment gave rise to an enhancement of CD71 antigen expression only, while prostaglandin E2 (PGE2) supplementation to culture media further decreased either CD25 or CD71 receptor induction. Interferon (IFN)-alpha and IFN-gamma treatment failed to modulate the frequency of CD25+ and/or CD71+ cells. Finally, the expression of CD71 receptor was increased by deferoxamine supplementation, this suggesting a partial involvement of iron overload in the depressed function. Although further studies are required to evaluate at a molecular level the decreased antigen expression, these findings indicate that several mechanism are involved in the elderly-related decline of T lymphocyte activation structures during lectin stimulation.

Aged↗

Effects of acetyl-L-carnitine oral administration on lymphocyte antibacterial activity and TNF-alpha levels in patients with active pulmonary tuberculosis. A randomized double blind versus placebo study.

Acetyl-L-carnitine (ALC), a drug for the treatment of ageing-related neuroendocrine dysfunctions, was orally administered--2 gm/day for 30 days--to 10 patients with active pulmonary tuberculosis (TBC). Lymphocyte-mediated antibacterial activity and serum levels of tumor necrosis factor (TNF)-alpha were evaluated before and after treatment, comparing the values with those of 10 TBC patients receiving placebo. Results show that by day 30, antibacterial activity remained unmodified or increased in ALC-treated subjects, while decreased in the placebo group. No influence of ALC on TNF-alpha levels was detectable. These data suggest that the host's immune responses to M. tuberculosis infection can be selectively modulated by drugs acting on the neuroendocrine axis.

Acetylcarnitine↗

Clinical and immunologic effects of combination therapy with intravenous immunoglobulins and AZT in HIV-infected patients.

30 patients with HIV infection were enrolled to evaluate the clinical efficacy and toxicity of zidovudine (AZT), 0.5 g/day p.o. (Group A) vs. AZT 0.5 g/day p.o. plus intravenous immunoglobulins (IVIG), 0.4 g/kg of body weight for three consecutive days, followed by one treatment of 0.6 g/kg of body weight every fourth week (Group B), over a period of one year. The study was open and randomized. The treatment groups were compared using the following study variables: 1) type of infections, recurrences and severity; 2) change in CD4+ T and CD8+ T cell count; 3) change in platelet count; 4) change in TNF alpha serum levels; 5) the probability of not developing an opportunistic infection over a period of 12 months. Patients from Group B developed less pathological events in comparison to Group A. No significative differences were evident with regard to values of T cell subsets obtained before and after treatment in each group and between the two groups. On the contrary, in 12 out of 15 patients from Group B there was a significant increase in platelet count. In both groups there was a significant decrease of mean serum levels of TNF alpha when a comparison was made between time 12 vs. time 6. However, when data were expressed as single values, in three subjects from Group B TNF alpha was still detectable by time 12 vs. 9 individuals in Group A. The cumulative probabilities of developing an opportunistic infection over the 12 months of treatment in the Group A subjects were significantly higher than in the Group B subjects (p less than 0.01). Adverse effects--nausea and gastric pain--were reported for 3 individuals (20%) from Group A and 4 patients (26%) from Group B. In conclusion, patients treated with AZT are especially likely to benefit from IVIG prophylaxis.

Adult↗