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Biomedical subjects

F Capsoni

Publications and source records attributed to F Capsoni.

At least 37 records · Page 2Linked to original sources

Immunomodulation of polymorphonuclear leukocytes by D53 Immucytal and its constitutive fractions.

D53 (Immucytal) is a compositive vaccine made of immunogenic ribosomes extracted from 4 bacterial species (Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae) associated with a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (MPG-Kp). In this work we have studied the effect of the compound on human polymorphonuclear leukocyte (PMN) function "in vitro". We have demonstrated that D53 was able to significantly increase Fc- receptor dependent phagocytosis without modify the C3-receptor dependent activity. Furthermore D53 enhanced the oxidative metabolism (evaluated by chemiluminescence) both using cells in resting conditions or after stimulation with phagocytable or soluble stimuli. On the contrary D53 caused a dose-dependent inhibition of PMN migration toward different chemoattractants. Using the two constitutive fractions of the compound (ribosomes and proteoglycans) we have observed that the MPG-Kp component was mainly responsible for the modulating activity of the drug on human PMNs.

Adjuvants, Immunologic↗

In vitro modulation of human monocytes functions by RU 41740 (Biostim).

The in vitro effects of RU 41740, a mixture of two glycoproteins extracted from K. pneumoniae and possessing immunomodulatory activity, on human monocyte's cytotoxic activity, migratory capacity and monokine production were investigated. Exposure to RU 41740 in nanogram concentrations was associated with rapid increases in IL-1 and TNF production and marked augmentation in the monocytes' killing of TNF-sensitive targets, whereas killing of TNF-insensitive targets required longer exposures to microgram concentrations of this drug. Using otherwise effective treatment conditions, RU 41740 did not directly affect monocyte's spontaneous and FMLP-induced migration. The possible role of mononuclear cells stimulation and increased production of effector and regulatory monokines in the immunomodulatory activity of this product is addressed.

Adjuvants, Immunologic↗

In vitro and ex vivo effect of RU41740 on human polymorphonuclear leukocyte function.

We investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae and possessing immunomodulating properties, on human neutrophil functions in vitro and ex vivo. Our in vitro results showed that RU41740 increased complement- and Fc receptor-dependent phagocytosis. Moreover, the drug enhanced the oxidative metabolism (assessed by chemiluminescence) both in resting and stimulated cells; in the latter case the RU41740-induced enhancement was observed when neutrophils were stimulated with opsonized particles of N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not when phorbol myristate acetate was used. Using otherwise effective experimental conditions, RU41740 did not affect spontaneous or FMLP-induced neutrophil migration. For the ex vivo experience we tested neutrophils of ten elderly subjects with a previously demonstrated phagocytic defect. These subjects were treated orally with RU41740 at a daily dose of 2 mg for 1 week during the first month, and of 1 mg for 1 week in the second month. In this population, RU41740 was able to restore the impaired phagocytic activity and to induce a significant increase of spontaneous chemiluminescence (CL); stimulated CL was also positively influenced. These effects on neutrophils provide new explanatory bases for the immunostimulatory activity of RU41740.

Adjuvants, Immunologic↗

Modulation of human polymorphonuclear leukocyte function by the flavonoid silybin.

The effect in vitro of the naturally occurring flavonoid silybin on human polymorphonuclear leukocyte (PMN) functions has been studied. Preincubation of PMNs for 10 min at 37 degrees C with silybin inhibited, in a dose-dependent way, the luminol-enhanced chemiluminescence (CL) generated by stimulated cells without affecting the non-enhanced CL or superoxide anion production evaluated by the cytochrome C reduction assay. No significant effect of silybin on PMN phagocytic or chemotactic activities were found. Silybin did not absorb light at the wavelength of luminol-enhanced CL and was not toxic to PMNs at the concentrations used. Catalase, a scavenger of H2O2, inhibited luminol-enhanced CL to a similar degree as silybin; moreover, when incubated together with PMNs, silybin and catalase did not produce an additive inhibition of CL. On the contrary, the simultaneous addition of silybin and sodium azide, an inhibitor of myeloperoxidase, further increased inhibition over that seen with azide alone. These results suggest that inhibition of H2O2 may be the mechanism by which silybin inhibits the luminol-enhanced CL generated by stimulated PMNs. Such results indicate a possible anti-inflammatory activity for silybin even if their clinical relevance remains to be elucidated.

Azides↗

Inhibition of neutrophil oxidative metabolism by nimesulide.

Oxygen derived free radical release from activated neutrophils may be in part responsible of tissue damage in the acute phase of inflammation. We have shown that the methane sulfonanilide antiinflammatory agent nimesulide inhibits the respiratory burst of phagocytosing neutrophils without affecting their phagocytic or chemotactic responsiveness. In fact, chemiluminescence and superoxide anion generation by polymorphonuclear leukocytes (PMN) stimulated with zymosan particles or with the synthetic peptide FMLP are inhibited by nimesulide and its 4-OH metabolite in a dose dependent fashion without affecting cell viability. The control of the extracellular flux of radical species by pharmacological compounds may affect the course of inflammation reducing tissue damage. Our data suggest that the inhibition of superoxide anion production by neutrophils is an additional mechanism of action of the antiinflammatory agent nimesulide.

Anti-Inflammatory Agents, Non-Steroidal↗

Immunomodulating activity of RU 41740: in vitro and in vivo studies on human lymphocytes.

A group of institutionalized elderly subjects, selected on the basis of their skin hypoergy and displaying different kinds of T and B lymphocyte impairments has been chosen as a model to verify the in vivo immunopotentiating activity of RU 41740 on human lymphocytes. Oral treatment with the drug was able to: restore or improve the cutaneous delayed hypersensitivity to recall antigens; significantly increase the blastigenetic response to mitogenic and submitogenic doses of PHA and PWM and improve the in vitro PWM-induced synthesis of IgG and IgM. The immunopharmacological activity of RU 41740 appeared to persist three months after the end of therapy, without any direct stimulating activity on the peripheral blood lymphocytes. The in vitro results seem to suggest that peripheral lymphocytes are not directly influenced by the drug.

Adjuvants, Immunologic↗

Effect of pirprofen on polymorphonuclear leukocyte functions in vitro.

The action of the new non-steroidal anti-inflammatory drug (NSAID) pirprofen on different functions of human polymorphonuclear leukocytes (PMNs) has been studied. The chemotaxis of PMNs was found to be affected by pirprofen in a dose-dependent fashion; at a concentration of 2 micrograms/ml (10 times lower than the therapeutic blood levels) it significantly inhibited PMN locomotion toward two different chemoattractants. Moreover pirprofen inhibited the chemiluminescent response in a dose- and stimulus-dependent way. In fact the drug inhibited the chemiluminescence induced by the soluble stimuli FMLP or PMA, but it was ineffective when zymosan particles were used. The phagocytosis and adhesion functions of the PMNs were not modified by pirprofen at the concentrations tested. These experimental results suggest that a reduction of the accumulation and activation of inflammatory cells in tissues may represent another way, together with cyclooxygenase inhibition, by which pirprofen realizes its antiinflammatory activity in vivo.

Cell Adhesion↗

Defective granulocyte chemotaxis and natural killer activity in a patient with recurrent infections.

A 25-year-old male with a history of recurrent infections presented with fever, severe aplastic anaemia, splenomegaly and retroperitoneal node enlargement. Lympho-histiocytic granulomas were found in spleen, liver and lymph nodes. Granulocyte studies revealed normal morphology, severely impaired random migration and complete absence of directed locomotion. Whereas phagocytosis was slightly reduced, candidacidal activity and nitroblue tetrazolium reduction were normal. Basal granulocyte cyclic GMP levels were within the normal range while a 5-fold increase of cyclic AMP levels was observed. Numerous abnormalities were also found in the patient's lymphocytes: lack of delayed hypersensitivity, reduced response to mitogens, low OKT4/OKT8 ratio, absence of natural killer (NK) activity with normal number of cells recognized by NK-specific monoclonal antibodies. These observations describe a distinct clinico-pathologic entity and suggest the possibility of a common defect in granulocytes and in NK cells.

Adult↗

A study of cellular immunity in newborns after prevention of respiratory distress syndrome (RDS).

Cellular immune responsiveness against infections was evaluated in four groups of newborns. The first group was composed of preterm newborns whose mothers had received betamethasone for prevention of RDS, the second group of preterm newborns whose mothers had received ambroxol for prevention of RDS, the third group of preterm newborns whose mothers had not received any drug enhancing surfactant production, and the fourth group were healthy-term infants. A reduction of OKT4+ cells and functional deficits of neutrophils were found in preterm infants born to mothers treated with steroids, whereas no functional abnormalities of immune-competent cells were observed in preterm infants born to mothers treated with ambroxol.

Ambroxol↗

Chronic granulomatous disease in a 23-year-old female.

A 23-year-old girl with clinical and laboratory findings characteristic of chronic granulomatous disease is described. The patient was admitted to hospital because of severe disseminated aspergillosis. Studies of neutrophils showed normal phagocytosis but impaired microbicidal killing and a failure of the respiratory burst activity as measured by NBT-reduction, superoxide generation, chemiluminescence and antibody-dependent cell mediated cytotoxicity. Patient's neutrophils had normal chemotactic responsiveness but a marked impairment in the level of serum chemotactic activity was observed. Neutrophils from the parents and 2 maternal aunts showed normal values for all the determinations. The lack of evidence for a carrier state in all the family members studied together with the inability to detect a mixed population of neutrophils in our patient are in contrast with the Lyon's hypothesis of X-chromosome inactivation. Our findings suggest an autosomal recessive inheritance in this female with chronic granulomatous disease.

Adult↗

Phagocyte function and immunological findings in a Wiskott-Aldrich syndrome long-term survivor.

The case reported concerns a 19-year-old man who presented with clinical and laboratory findings compatible with the Wiscott-Aldrich Syndrome. Our patients is the eighth reported case of a long-term survivor with this syndrome. Immunologic studies revealed, in spite of a normal lymphocyte number, an impaired delayed hypersensitivity and a failure of response to mitogens and irradiated allogeneic cells. IgE and IgA levels were high while IgM levels were low. Studies of phagocytic cells showed normal phagocytosis, candidacidal activity, IgG receptors and phagocytic metabolic burst. However, the patient's neutrophils and monocytes responded poorly to chemoattractants and the serum generated less chemotactic activity than normal sera. Detailed studies revealed the presence in the patient's serum of 2 different inhibitors of chemotaxis: a cell-directed inhibitor and an inhibitor of chemotactic factors.

Adult↗

Effect of ambroxol on human phagocytic cell function.

The in vitro effects of ambroxol on phagocytic and microbicidal activities of human neutrophils and monocytes have been studied. Preincubation of neutrophils with ambroxol (10 to 100 ng/ml) had no effect on their phagocytic or microbicidal capacities. On the other hand, when monocytes were preincubated for 24 hours with ambroxol a significant increase of their microbicidal activity was observed, without effect on the phagocytic properties.

Ambroxol↗

Immune function and renal transplantation in Fabry's disease.

A deficient leucocyte immunological function could cause the reported high rate of lethal infections following renal transplantation in patients affected by Fabry's disease. We have studied humoral immunity, peripheral lymphocyte subsets, mitogenic lymphocyte response in vitro and granulocyte function in three patients with Fabry's disease. The immunological state appears to be quite similar to that of the uraemic population in general, not showing any specific impairment.

Fabry Disease↗

Neutrophil chemotactic factor of anaphylaxis (NCF-A) release in aspirin-induced asthma.

Neutrophil chemotactic activity (NCA) following oral challenge with aspirin (ASA) was determined in ASA-intolerant asthmatic subjects, and in ASA-tolerant asthmatic and normal subjects. There was a statistically significant fall in FEV1 and a rise in NCA (P less than 0.01) following challenge in the ASA-sensitive subjects compared with that of the ASA-tolerant subjects and normal controls. No significant difference was observed between the latter two groups. The chemotactic factor identified in this study had a molecular weight greater than 150 000 which is consistent with NCF-A (neutrophil chemotactic factor of anaphylaxis). The ASA-induced fall in FEV1 and rise in NCA was further studied in three of the ASA-intolerant asthmatic subjects, with and without pretreatment with inhaled sodium cromoglycate. In these subjects, the drug inhibited both the oral ASA-induced bronchoconstriction and the increase in neutrophil chemotactic activity. These results suggest that ASA-induced asthma involves mediator release from mast cells, as shown by the increase in NCA following ASA challenge and the protective effect of sodium cromoglycate which is considered to inhibit mast-cell degranulation.

Adult↗

Effect of corticosteroids on neutrophil function: inhibition of antibody-dependent cell mediated cytotoxicity (ADCC).

Hydrocortisone sodium succinate (HC) inhibited "in vitro" neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC). The drug effect was dose-dependent and completely reversible. The killing defect was partially overcome by increasing the density of the antibody on the target cells. However, HC added after the binding between effector and target cells was still able to inhibit in a similar dose-dependent way the cytotoxic activity. Our results suggest that HC interferes in a later step, after the effector/target interaction. Methyl-prednisolone and dexamethasone as well as HC were found to inhibit in a dose-dependent manner the neutrophil-mediated ADCC, whereas testosterone did not have any effect.

Adrenal Cortex Hormones↗

Defective suppressor cell activity in essential mixed cryoglobulinemia.

Peripheral blood mononuclear cells from patients with essential mixed cryoglobulinemia were investigated for the ability to induce suppressor cell activity (S.C.A.) following in vitro exposure to Concanavalin A (Con A). The generation of Con A-S.C.A. is significantly impaired in essential mixed cryoglobulinemia compared to the healthy controls. No correlation was found between Con A-S.C.A. and the clinical or laboratory parameters of the disease. This impaired ability to induce Con A-S.C.A. in essential mixed cryoglobulinemia reflects a functional T-cell defect, which may play a role in the pathogenesis of the disease.

Adult↗

Phagocytic function of polymorphonuclear leukocytes in essential mixed cryoglobulinaemia.

We have studied the phagocytic function of polymorphonuclear leukocytes obtained from 16 patients with essential mixed cryoglobulinaemia and 16 normal subjects, utilizing three different experimental models. The in vitro phagocytosis of Candida albicans by polymorphonuclear leukocytes obtained from the patients in the presence of autologous serum was subnormal as compared with controls (p less than 0.002). The neutrophil defect appeared to be cellular since: a) no effect of the patient's serum on the phagocytic capacity of normal neutrophils was demonstrable; b) the defect was not reversed when normal AB serum was used as opsonin source. The polymorphonuclear leukocytes from the same patients ingested IgG-coated sheep red blood cells to a significant higher degree than normals (p less than 0.002) when tested in patient's serum free-medium. Finally, no differences between patients and controls were observed on the basis of latex uptake. A possible explanation for these contradictory results is discussed.

Adult↗