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Biomedical subjects

M Provinciali

Publications and source records attributed to M Provinciali.

At least 37 records · Page 2Linked to original sources
PubMed1996

Natural cytotoxicity and GnRH agonist administration in advanced endometriosis: positive modulation on natural killer activity.

OBJECTIVE: To investigate the effects of pharmacologic suppression of ovarian function on the immune system, with respect to the clinical outcome of endometriosis and the possibility of an immunoendocrine combined treatment. METHODS: After informed consent, 25 of 37 patients with revised American Fertility Society stage III and IV endometriosis who underwent postoperative medical treatment were selected and enrolled for this immunoendocrine longitudinal study. Medical treatment consisted of tryptorelinum depot injection, 3.75 mg/month for 24 weeks. Blood samples were collected before the first injection in the early follicular phase, day 2-3 of the cycle, and during medical treatment (every 4 weeks) and follow-up (every 6 months). At the end of the study, we had ten blood samples per patient to evaluate the cytotoxic activity, the number of natural killer cells, and the serum levels of estradiol. Natural killer activity was determined against the K562 cell line by target cell retention of the fluorescent dye carboxyfluorescein diacetate. RESULTS: A positive immunomodulating effect was observed during GnRH agonist administration. In particular, a significant progressive increase in natural killer cell activity was defined within the first 12 weeks of medical treatment; after three injections, we observed the highest values of cytotoxicity, with a median of 7.1 lytic units (range 0.3-14.0; P = .02). Natural cytotoxicity then decreased toward a plateau, which persisted during therapy completation and follow-up, with slight fluctuations. In patients who had recurrence, the values of natural killer cell activity were constantly lower than those in patients with disease-free follow-up, particularly within the first 12 weeks of medical treatment.

Adult↗
PubMed1996

Role of prolactin in the modulation of NK and LAK cell activity after short- or long-term morphine administration in neoplastic patients.

In a previous work we demonstrated that chronic in vivo antalgic therapy of cancer patients with morphine reduced the endogenous cytotoxic activity of natural killer (NK) cells, while increasing the development of lymphokine activated killer (LAK) cell cytotoxicity. In order to investigate the mechanisms by which morphine affects NK and LAK cell function further, we evaluated the modulation exerted by short- or long-term morphine administration on either NK/LAK cell cytotoxicities or plasma levels of prolactin (PRL) and other immunomodulating neurohormones. An intravenous morphine injection (10 mg) significantly increased the plasma levels of PRL, reduced the cytotoxic activity of NK cells, and increased the development of LAK cell activity 30 min after drug injection in neoplastic patients. The administration of bromocriptine before the injection of morphine prevented both PRL augmentation and the increase in LAK cell activation, although it did not prevent the inhibition of NK cytotoxicity. The chronic oral administration of morphine (90 +/- 30 mg/day for 1 month) also resulted in higher PRL levels; the NK and LAK cell activities were, respectively, lower than or higher than those found in neoplastic patients untreated with morphine. The plasma levels of thyrotropin (TSH), adrenocorticotropic hormone (ACTH) and cortisol were not significantly modified in either short- or long-term experiments. The absolute number and the percentages of lymphocyte populations, as well as the percentage of IL-2 receptors, were not modified after short-term morphine administration whereas little changes of T lymphocyte populations and NK cell number were observed after oral treatment with morphine. In vitro morphine did not affect the development of LAK cell activity. In conclusion, our findings indicate that morphine reduces NK cytotoxicity and increases the development of LAK cell cytotoxicity after short- and long-term administration. The effect of morphine on LAK cell activation but not on NK cell reduction is related to the modulation of PRL levels determined by the opioid drug.

Analgesics, Opioid↗
PubMed1996

Prolactin increases the susceptibility of primary leukemia cells to NK and LAK effectors.

Our previous studies have shown that prolactin (PRL), a pituitary and lymphocyte hormone and a ligand of the cytokine/hemopoietin receptors (R) superfamily, acts synergistically with interleukin (IL)-2 on the development of lymphokine activated killer (LAK) cells and enhances the effects of GM-CSF and IL-3 on myeloid progenitors' proliferation and differentiation. More recently, we have demonstrated that GM-CSF and IL-3 increase the sensitivity of acute myeloid leukemic (AML) cells to LAK activity. Together, these findings have prompted us to study the role of PRL on the target arm of the LAK response. We show here that CD33+ blasts from AML patients express membrane PRL-R and that the PRL/PRL-R interaction is followed by increased susceptibility to natural killer (NK) (p < 0.02) and LAK (p < 0.001) cells. As predicted from the dimerization model of PRL-R and in agreement with previous reports, the response of AML blasts to PRL was bell-shaped with a trend peak at 25 ng/ml. Although enhanced lysis occurred at the target recognition level, it was not accompanied by changes in the MHC class I, cellular adhesion molecules, or myeloid differentiation antigens. Cell cycle recruitment and lysis increased concurrently in three cases studied, suggesting a modulatory action of PRL on the expression of putative cycle-related NK/LAK-target structures. Together, these data strengthen the role of PRL in the LAK response.

Adjuvants, Immunologic↗
PubMed1995

Role of the low zinc bioavailability on cellular immune effectiveness in cystic fibrosis.

An altered cellular immune response as a secondary phenomenon has been suggested to be probably involved in the bronchopulmonary infections by Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary infections has led us to further investigate the possible existence of other cellular immune defects and their cause. Alterations in zinc turnover are present in CF. Zinc is relevant for good immune functioning. In particular, zinc is required to confer biological activity to thymulin (ZnFTS), a biochemically defined thymic hormone with a modulating action on cell-mediated immunity. The zinc-unbound form (FTS) is inactive and it can be unmasked by in vitro zinc addition to the plasma samples revealing the total amount of circulating thymulin (active + inactive). Marginal zinc deficiencies may prevent peripheral biological activation of active thymulin. Total zinc-saturable thymulin fractions in CF are similar to those observed in normal subjects, whereas the active quota is strongly reduced associated with concomitant high plasma levels of inactive thymulin compared to the values of healthy children (P < 0.01). A strict correlation exists between zinc and thymic hormone-saturable fraction (r = 0.87, P < 0.01) in CF. These findings suggest that the defect is not due to a thymic failure but to a reduced peripheral saturation of thymulin by zinc ions. This defect might depend on augmented plasma concentration of alpha 2-macroglobulin, which has a higher binding affinity for zinc than thymulin. T cell subsets are normal in CF. Reduced NK cell number and activity are present. Also, plasma IL-2 levels are reduced. The existence of positive correlations between zinc and IL-2 (r = 0.79, P < 0.01) and between zinc or active thymulin and NK activity (r = 0.70, P < 0.01 and r = 0.88, P < 0.01, respectively) suggest a close link among zinc failure, impaired IL-2 activity, low thymulin level, and reduced NK activity in CF patients with both normal and growth retardation. Although the role of NK cells is unknown in CF, a zinc supplementation, in order to induce a complete saturation of thymulin molecules, to correct some cellular immune defects and to improve the growth, may be suggested.

Adolescent↗
PubMed1995

Relationship between 17-beta-estradiol and prolactin in the regulation of natural killer cell activity during progression of endometriosis.

Endometriosis is an estrogen-dependent disease affecting women during their reproductive years. An abnormal immune function and, in particular, a decreased natural killer (NK) cell activity have been found in endometriosis, suggesting a role of the immune system in the pathophysiology of the disease. We have recently evidenced a significant inverse relationship between 17-beta-estradiol plasma levels and NK cytotoxicity in endometriosis patients. In this study we have investigated the combined role of 17-beta-estradiol (E2) and prolactin (PRL) in the regulation of NK cell activity during the progression of endometriosis, by evaluating the correlation among E2, PRL, and other immunomodulating neurohormones on both the cytotoxic activity and the number of NK cells in women at different stages of endometriosis. The early stages (I/II) of endometriosis are characterized by increased plasma levels of either E2 or PRL without significant alterations of NK cell activity in comparison with healthy subjects. The progression to advanced stages (III/IV) of the disease is associated with a further increase of E2 levels, a decrease of PRL plasma concentrations (with an increase of E2/PRL ratio), and an impairment of NK cytotoxicity. The plasma levels of both E2 and PRL and the E2/PRL ratio are significantly correlated with the values of NK cytotoxicity in advanced stages of endometriosis. Either the absolute number or the relative percentage of CD16+ or CD56+ peripheral lymphocytes are not significantly different between patients at either stages I/II or III/IV and healthy controls. Plasma levels of progesterone (P) and luteinizing hormone (LH), are not significantly changed in different stages of endometriosis with respect to healthy controls. The significant decrease of follicle-stimulating hormone (FSH) plasma levels found in either stages I/II or III/IV endometriosis patients is not correlated with the NK cell activity. In conclusion, at advanced stages of endometriosis the impairment of NK cell activity occurs with increased E2, and decreased PRL plasma levels. Additional studies are required to determine whether the E2/PRL ratio represents a possible biochemical marker of endometriosis.

Adult↗
PubMed1995

Dose-dependent opposite effect of zinc on apoptosis in mouse thymocytes.

Zinc is a crucial nutritional component required for the normal development and maintenance of immune functions. It has been reported that zinc is a potent inhibitor of DNA fragmentation, the specific marker of apoptosis. The effect of zinc on apoptotic cell death has been previously studied in a narrow range of high zinc concentrations, and the role of physiological zinc doses has not yet been elucidated. In this paper we evaluate the effect of in vitro Zn2+ administration at concentrations higher than, corresponding to, and lower than the physiological concentration, in thymocytes from young mice. We demonstrate that Zn2+ has an opposite effect on apoptosis, inhibiting or increasing it depending on the Zn2+ concentration used. High Zn2+ concentrations (from 600 to 75 microM) inhibit both serum-free medium and DEX-induced thymocyte apoptosis. Low Zn2+ concentrations (from 15 to 7.5 microM) induce apoptosis or increase serum-free medium-induced apoptosis. The effect of low Zn2+ concentrations on DEX-induced apoptosis is dependent on the length of incubation, since Zn2+ has an additive effect with DEX in inducing DNA fragmentation at 8 h of culture, whereas it blocks DEX-induced apoptosis after 20 h incubation. Both DEX and 15 microM Zn(2+)-induced DNA fragmentation require protein synthesis, being blocked through cycloheximide. The inhibiting and inducing effects of Zn2+ on apoptosis are exerted on G0/G1 phase thymocytes. The inhibiting effect of Zn2+ on apoptosis is related to an increase in the number of CD4+CD8+ thymocytes. Concentrations of Zn2+ inducing apoptosis sometimes cause a decrease of CD4+CD8+ cells with a corresponding increase of CD4+CD8-thymocytes. These data show that in vitro Zn2+ has a dose-dependent opposite effect on apoptosis, suggesting that Zn2+ not only acts as an inhibitor but also plays a more complex role in physiological intrathymic cell selection.

Analysis of Variance↗
PubMed1995

Pituitary-thyroid axis and immune system: a reciprocal neuroendocrine-immune interaction.

A good body of experimental and clinical results has supported the existence of numerous reciprocal interactions among the nervous, endocrine and immune systems. Increasing evidence has been accumulated in the last years on the interaction between pituitary-thyroid hormones and the immune system on the basis of either the existence of receptors for thyreotropic and thyroid hormones on lymphocytes or the frequent immune alteration in physiological and pathological fluctuations of thyroid hormones. The data were obtained either in animals with experimentally induced hyper- or hypothyroidism or in humans with various hyperthyroid or hypothyroid situations. Conversely, immune-derived products such as lymphokines and monokines have been shown able to influence the pituitary-thyroid axis modulating either the thyroid hormone levels or the hormone/cytokine production by thyrocytes. The present paper aims at summarizing the data available on the existence of thyroid-immune interactions, and at analyzing the possible integration between pituitary-thyroid hormones and immune factors in favoring the development and maintenance of both thymic and peripheral immune efficiency. The relevance of pituitary-thyroid-immune interactions is discussed for its implication in the ageing process.

Aging↗
PubMed1995

Natural killer activity in stage III and IV endometriosis: impaired cytotoxicity and retained lymphokine responsiveness of natural killer cells.

Our objective was to investigate the role of estrogens in the development and progression of endometriosis, and evaluate the in vitro boosting effect of lymphokines on the activity of natural killer cells from endometriosis patients, with respect to the estradiol concentrations. Natural killer activity of peripheral blood was evaluated in 42 endometriosis patients who underwent laparoscopy for pelvic pain, infertility and benign adnexal masses, and it was correlated with serum estradiol levels. Twenty-five women with moderate and severe disease were re-evaluated for immune and endocrine parameters 4-8 weeks after surgery, before any specific adjuvant medical treatment, and analyzed for in vitro responsiveness of cytotoxic cells to interferon (IFN) alpha 2 beta and interleukin-2 (IL-2) incubation. Patients with moderate and severe endometriosis showed a significant decrease of natural cytotoxicity when compared with patients with mild and minimal disease (p = 0.01). The decrease of immune reactivity was independent of a reduced representation of natural killer cells, and persisted after surgical removal of all macroscopic endometriosis foci. A significant inverse relationship was observed between natural killer activity and serum estradiol levels, which resulted in moderate and severe disease (r = -0.4, p = 0.009) but not in stages I and II. The in vitro responsiveness of cytotoxic cells to lymphokine incubation was preserved; both IFN alpha 2 beta and IL-2 were able to increase the cytotoxicity of natural killer cells significantly from advanced-stage patients (p = 0.014 and p = 0.006 for IFN alpha 2 beta and IL-2 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Evaluation of lymphokine-activated killer cell development in young and old healthy humans.

The kinetics of the development of lymphokine-activated killer (LAK) cell activity, the surface phenotype, and the expression of p55 and p75 interleukin 2 receptors (IL-2R) on IL-2-activated peripheral lymphocytes have been investigated in young and old healthy humans selected according to the Senieur Protocol criteria. No difference is present between young and old healthy subjects in terms of LAK cell activity development. The proliferative capacity of lymphocytes incubated with IL-2 shows similar kinetics in young and old subjects. The mean percentages of CD56+ and CDl6+ cells reach higher levels in old than in young donors. The proportion of CD56+/CD25+ cells in culture is significantly higher in old than in young individuals. A progressive decrease of CD4+ population occurs during LAK cell development, both in young and old subjects. The proportion of CD4+ T cells in culture is lower in old than in young individuals. No age-related difference is present in the mean percentage of cells positive for p55 or p75 IL-2R at any culture time. Thus, our findings show similar kinetics of development of LAK cell activity in young and old subjects, indicating that aging per se does not represent an exclusion criterion of cancer patients from clinical trials of adoptive immunotherapy. A higher proportion of CD56+ and CDl6+ cells seems to be required in old subjects to obtain the same levels of LAK cell activity present in young age.

Adult↗
PubMed1994

Adjuvant effect of low-dose interleukin-2 on antibody response to influenza virus vaccination in healthy elderly subjects.

It is well known that immune efficiency is frequently deteriorated in elderly people. The age-diminished antibody response to T-cell dependent antigens, such as influenza virus antigens, may explain the low protection offered by influenza vaccination in the elderly population. To investigate the possibility of increasing the antibody response to influenza virus vaccinations, we have conducted a nursing home-based study on the efficacy of IL-2. Seventy-five institutionalized elderly subjects (82 +/- 8 years) were enrolled in the study in the course of winter season 1991-1992. Thirty-nine subjects were treated with three subcutaneous daily injections of interleukin-2 (IL-2, 1 x 10(6) I.U./day) before vaccination and their antibody response was compared to that of 36 aged people receiving the vaccine only. An increased antibody response against influenza virus was present in vaccine plus IL-2 treated subjects (P < 0.001) but not in subjects treated with vaccine only. The number of protected subjects 45 days after vaccination was increased only in the IL-2-treated group (P = 0.045). The low-dose of IL-2 administered and the short-term treatment allowed a good tolerance to the IL-2 injection. In conclusion, the low-dose IL-2 treatment represents an effective means of inducing antibody response to influenza virus antigens in elderly subjects without appreciable toxicity.

Adjuvants, Immunologic↗
PubMed1994

Immune enhancement by conditioning of senescent mice. Comparison of old and young mice in learning ability and in ability to increase natural killer cell activity and other host defense reactions in response to a conditioned stimulus.

It has been clearly demonstrated that immune responses may be conditioned in a manner similar to that of the classical Pavlovian experiments. Evidence of impaired immune function in aging has raised the question of whether psychological conditioning of an immune response can also be effective in old age. The knowledge that aged mice have decreased spleen cell natural killer (NK) activity and that NK cytotoxicity, at least in young mice, can be psychologically conditioned led us to explore in old mice the possibility of conditioning the response of NK cell activity using the odor of camphor as the conditioned stimulus (CS) and the injection of Poly I:C as the unconditioned stimulus (US). Young and old male mice were divided into five and six groups, respectively. They received the CS and/or the US in association (conditioning) trials (sessions 1-9). Mice were exposed to the camphor odor alone at 72 hours after the final association trial to observe the conditioning phenomenon (session 10). The group conditioned with Poly I:C and camphor and receiving the CS at session 10 showed statistically significant increases in spleen cell NK activity over those of the control groups that did not receive the CS treatment at session 10 (2.6- and 4.0-fold increase in young and old, respectively). Treatment with camphor odor alone had no effect on boosting NK cell activity. These findings demonstrate the possibility of conditioning immune responses in old age, offering a valuable tool for attenuating age-related immune deterioration in various species, including the human. In addition, these results again confirm highly significant immune enhancement by classical conditioning and extend previous findings from female mice to males as well.

Aging↗
PubMed1994

Influence of neoadjuvant polychemotherapy on natural killer cell activity in patients with locally advanced cervical squamous carcinoma.

Peripheral blood natural killer (NK) cell activity against K562 tumor line was monitored in 16 patients with locally advanced squamous cervical carcinoma (II and III FIGO stages) during neoadjuvant polychemotherapy (cisplatin at 80 mg/m2 and bleomycin at 30 mg/m2). There was a significant progressive decrease in NK activity during the three cycles of antiblastic treatment (P = 0.008) without significant depletion of NK cell (CD56 and CD16 monoclonal antibody positive cell percentage and absolute number). A significant relationship was shown between basal NK activity levels and response to polychemotherapy; in fact, nonresponder patients had a significantly lower mean value of NK activity before polychemotherapy than responders (P = 0.044). In conclusion, NK activity declines as a result of antiblastic therapy; although polychemotherapy reduces tumor spread, its antineoplastic action may be affected by this decreased immune reactivity.

Adult↗
PubMed1993

Natural killer cell activity in endometriosis: correlation between serum estradiol levels and cytotoxicity.

OBJECTIVE: To evaluate the correlation between natural killer cell activity and serum estradiol (E2) levels in patients with different stages of endometriosis. METHODS: Natural killer cell activity of peripheral blood lymphocytes and serum E2 levels were evaluated in 73 women who underwent laparoscopy for pelvic pain, infertility, and benign adnexal masses. RESULTS: The 33 patients (45%) with endometriosis showed a significant decrease in natural killer cell activity in relationship to an increase in disease stage (correlation coefficient r = -0.83, P < .001). A significant inverse relationship was observed between cytotoxicity and serum E2 levels (correlation coefficient r = -0.89, P < .001). CONCLUSION: The relationship between natural killer cell activity and serum E2 levels suggests that an immunoendocrine interaction plays an important role in the progression of endometriosis.

Adult↗
PubMed1992

Optimization of cytotoxic assay by target cell retention of the fluorescent dye carboxyfluorescein diacetate (CFDA) and comparison with conventional 51CR release assay.

This paper describes the comparison between a fluorimetric NK assay based on the target cell retention of fluorescent dye carboxyfluorescein diacetate (cFDA) and standard 51Cr release assay. The results provide several suggestions to improve the cytotoxic assay based on the use of the fluorogenic substrate showing that the measurements of cFDA retained by target cells represent a method of evaluating cytotoxicity completely comparable to the 51Cr release assay.

Chromium Radioisotopes↗
PubMed1992

Improvement in the proliferative capacity and natural killer cell activity of murine spleen lymphocytes by thyrotropin.

In the present study we investigated the effect of thyrotropin (TSH) on both the proliferative capacity and the natural killer (NK) cell activity of murine spleen lymphocytes. It was found that TSH at various concentrations significantly increased the proliferative response of mouse lymphocytes to both concanavalin A (Con A) and phytohemagglutinin (PHA). This increase was particularly evident when suboptimal concentrations of mitogens were used (40-50% increase). The administration to cell cultures of TSH alone could not induce a significant stimulation of proliferative capacity. In order to provide a better knowledge about the mechanism by which TSH improved the mitogen-induced lymphocyte proliferation, the effect of the pituitary hormone on lymphocytes directly stimulated with recombinant interleukin-2 (RIL-2), was examined. It was observed that there was a great increase in IL-2-induced lymphocyte proliferation by TSH. The improvement in proliferative capacity of lymphocytes was particularly evident by using suboptimal rIL-2 concentrations (25-30% increase). The studies carried out on the cytotoxic activity of NK cells showed that TSH was able to significantly increase the IL-2-induced NK cell activity without modifying the basal levels of cytotoxicity. The results support the immunoregulatory role of TSH and contribute towards understanding the mechanisms of interaction between neuroendocrine and immune systems.

Animals↗