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N Fabris

Publications and source records attributed to N Fabris.

At least 19 recordsLinked to original sources
PubMed1992

Biomarkers of aging in the neuroendocrine-immune domain. Time for a new theory of aging?

A common and generally accepted assumption is that with advancing age, the thymus undergoes progressive and irreversible involution. This is considered the main cause for the age-related deterioration of various immune functions and, ultimately, for the increased incidence of infectious, neoplastic, and automimmune diseases in old age. This assumption is no longer tenable because of several clear-cut demonstrations that age-related thymic involution is not an intrinsic and irreversible phenomenon. Various neuroendocrine or nutritional manipulations can to induce a regrowth of the thymus, even when applied in old age. This thymic reconstitution is followed by a consistent recovery of peripheral immune functions. These data strongly support the idea that thymic involution is a phenomenon secondary to age-related alterations in neuroendocrine-thymus interactions and that it is the disruption of such interactions in old age that is responsible for most of the age-associated dysfunctions. On the basis of this experimental and clinical evidence and as an alternative to purely immune or neuroendocrine theories of aging, a neuroendocrine-immune hypothesis is proposed. Further work is required to determine if the age-related disruption of neuroendocrine-immune interactions occurs because of progressive accumulation of stressor-dependent consequences at the level of one or the other system or if it may depend on a single common cause.

Aging↗
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↗
PubMed1992

In vitro restoration by thymulin of NK activity of cells from old mice.

Old mice show a reduced natural killer (NK) cell activity. Among the causes proposed to explain this defect, both intrinsic failure of NK cells or age-related alteration of microenvironmental factors relevant for NK function, have been taken into consideration. The findings reported in the present paper, demonstrate that thymic peptides, and in particular the facteur timique serique (FTS), more recently called thymulin (ZnFTS) in its zinc-bound form, whose production and activity is generally reduced in old age, is able, when administered in vitro, to restore the crippled NK cytotoxicity of spleen cells from old mice. Neither the zinc-unbound form of the hormone (FTS) nor zinc ions alone are effective. The action is exerted on the basal NK activity and not on IFN-boosted NK cytotoxicity, at variance with the restoration obtained in similar experimental conditions with thyroid hormones, thus suggesting that different mechanisms or maturative steps of NK cells are involved.

Aging↗
PubMed1992

Natural killer cell activity in patients with gynecologic malignancies: correlation with histologic grading and stage of disease.

Basal natural killer (NK) cell activity in peripheral blood lymphocytes (PBLs) of 29 patients with gynecologic malignancy and 10 healthy controls was performed using K 562 cell line. A significant decrease of NK cell activity was observed in patients with gynecologic malignancy (p = 0.003). The NK cell activity of patients with poorly differentiated tumor or with stage IV of disease was significantly reduced with respect to patients at any other lower grade or earlier stage. We conclude that in patients with gynecologic malignancies there is a decrease of basal NK cell activity of PBLs, which is more significant in cases of distant tumor dissemination or poorly differentiated tumor (p less than 0.001).

Adult↗
PubMed1992

Lymphocyte subset and NK activity in cervical intra-epithelial neoplasia.

We have studied the systemic T-lymphocyte subset and, in particular, the natural-killer (NK) activity in 23 patients with cervical intra-epithelial neoplasia (CIN), and 11 controls (a history of normal cervical PAP smears and colposcopy patterns). The lymphocyte phenotypes were studied using a panel of monoclonal antibodies, and NK activity was evaluated as the percentage lysis of K 562 target cells. In patients with CIN we found a significant decrease in NK activity (p = 0.002) which was directly correlated with the grade of CIN, with no alterations in the absolute number of NK cells.

Adult↗
PubMed1992

Arginine-containing compounds and thymic endocrine activity.

The frequent association of malnutrition, infectious disease and aging has stressed the role played by some nutrients on the immune efficiency and particularly on the age-dependent immunological decline. Since arginine has been proven to enhance immune efficiency as demonstrated by the observation that supplemental dietary arginine accelerates would healing and increases thymus weight, we have evaluated the influence of oral administration of arginine on the age-associated immune deficiencies and in particular on the reduced thymic endocrine activity, as measured by the circulating level of one of the best known thymic peptides, i.e. thymulin. Thirty days oral treatment with arginine at the dose of 0.03 g/Kg b.w./day in 20 month old mice induces a full recovery of thymic endocrine activity and a significant increase of PHA responsiveness by spleen cells, when compared with untreated age-matched controls. In humans, oral administration of a commercially available arginine-lysin combination (Lysargin, Baldacci, Pisa, Italia) at the dose of 4 gr. of arg. + 4 gr. of Lysine induces a significant increment of thymulin blood level both in elderly and in cancer patients and at peripheral level, an increase of CD4+ lymphocyte subpopulation. These findings confirm the immunomodulation role of arginine and suggest that on the target of arginine as the thymus and particularly its endocrine activity. Furthermore arginine and arginine-containing compounds may offer a new therapeutical approach to restore thymic immunodeficiencies associated with age or secondary to pathologies inducing thymic deterioration such as trauma, stress and cancer.

Animals↗
PubMed1991

Zinc and bromocriptine long-term administration in patients with prolactinomas: effects on prolactin and thymulin circulating levels.

Several studies have demonstrated zinc (Zn), prolactin (PRL) and thymulin (Zn-FTS) interplay: Zn inhibits, in a dose related manner, PRL release from lactotropes in vitro and stimulates thymulin synthesis in vivo both in humans and in animals. PRL receptors are present on thymic epithelial cells (TEC); PRL stimulates TEC trophism and activity. Little is known about the influence of PRL on Zn metabolism, though in prolactinomas we found reduced Zn and thymulin circulating levels. For this reason, we evaluated PRL, Zn, bioactive thymulin (Zn-FTS) and total thymulin (T-FTS: Zn-bound plus Zn-unbound form) serum levels in 58 patients with prolactinomas (PRL: 253 +/- 263 micrograms/L), Zn (82 +/- 23 micrograms/dl), Zn-FTS (2.2 +/- 0.20 log2(-1] and T-FTS (3.7 +/- 0.25 log2(-1] were significantly lower (p less than .01) than those found in age matched controls. Zn-unbound bioinactive thymulin form (FTS) levels were in the normal range. Bromocriptine administration (Brc) (2.5-5 mg p.o., b.i.d. for 9 months) to 20 patients with microprolactinomas lowered serum PRL levels (10.5 +/- 6.2 micrograms/L) and significantly increased (p less than .01) Zn (118.6 +/- 14.7 micrograms/dl), Zn-FTS (3.96 +/- 0.7 log2(-1)) and T-FTS (4.66 +/- 0.7 log2(1)) circulating levels. ZnSO4 administration (400 mg p.o. daily for 3 months) to 6 patients with microprolactinomas, significantly increased (p less than .01) Zn (136 +/- 18 micrograms/dl), Zn-FTS (4.5 +/- 0.5 log2(-1)) and T-FTS (5.6 +/- 0.9 log2(-1)) levels, while caused only a slight decrease in serum PRL concentrations (from 95 +/- 8 to 75 +/- 9 micrograms/L; p: NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Evaluation of NK and LAK cell activities in neoplastic patients during treatment with morphine.

The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug.

Administration, Oral↗
PubMed1991

Thymic endocrine activity in children with idiopathic growth-hormone deficiency.

Experimental and clinical evidences suggest that thymic endocrine function is modulated by the neuroendocrine network and in particular by growth hormone. The plasma of thymulin has been found reduced in congenital hypopituitarism and increased in acromegalic conditions when compared with the values observed in age-matched controls. In the present paper we have investigated in congenital GH-deficient children the effect of one year therapy with GH on the plasma level of thymulin, IGF-1 and plasma zinc; this last parameter has been checked because zinc is required for thymulin activity and modulates IGF-1 production. The basal thymulin and IGF-1 values are lower in GH deficient children than age-matched controls whereas zinc levels show a slight reduction. GH therapy induces a significant increment both of thymulin and IGF-1 levels and a slight increase of plasma zinc. A positive correlation has been found between zinc values and thymulin activity but not between GH and thymulin. Whether the recovery of thymulin production in GH deficient children by GH therapy is mediated by IGF-1 or by bioavailability of zinc ions remains to be established.

Adolescent↗
PubMed1991

Recovery of spleen cell natural killer activity by thyroid hormone treatment in old mice.

The age-dependent changes in thyroid-hormone blood levels and the effects of in vivo and in vitro thyroid-hormone administration on both basal and lymphokine-induced spleen cell natural killer (NK) activities have been investigated in young and old Balb/c mice. Both thyroxine (T4) and triiodothyronine (T3) plasma levels decline progressively with increasing age of the mice, displaying in 25-month-old mice only 50 and 60% of the T4 and T3 blood levels, respectively, found in young mice. In vivo T4 administration to old mice causes a significant increment in endogenous NK activity (2.2-fold increase), which approaches the values observed in young animals, while it does not modify NK activity in young mice. The T4 injection in old mice does not induce changes in the lymphocyte sub-populations. When T4 is administered in vitro alone or in combination with interferon (IFN) and/or interleukin 2 (IL-2), no effect is observed either on basal activity or IL-2-induced cytotoxicity, whereas the IFN sensitivity of spleen cells from old mice is significantly recovered (4-fold increase). T4 is able to increase IFN-induced cytotoxicity even when administered in vitro simultaneously with IFN to the cytotoxic assay (1.5- and 2.7-fold increases in young and old mice, respectively). Under these conditions, IFN alone is not able to exert any boosting effect even at a young age. In vivo propylthiouracil (PTU) administration completely abrogates the IFN responsiveness of spleen cells in young mice. The interruption of the PTU treatment results in a recovery of IFN-inducible NK cytotoxicity. Taken together, our findings point out the important role of thyroid hormones in the modulation of NK cell activity and provide a new insight into the mechanisms by which the endocrine system is able to influence the expression of natural immunity.

Aging↗
PubMed1991

Reversibility of age associated NK defect by endocrinological and/or nutritional intervention.

Several abnormalities arise at the level of NK cell function in both rodents and humans with increasing age. The age-related changes are not irreversible alterations since they can be reversed either by endocrinological or nutritional approaches, suggesting that age-related microenvironmental changes may play a relevant role in the age-related immune deterioration. Whether endocrine and nutritional factors have an additive effect or act through the same intracellular mechanisms remains to be established, though the first possibility seems more likely since the action of TSH and thyroid hormones is specifically directed towards lymphokine-boosted NK activity, while AL are able to prevent age-associated defect of basal NK cytotoxicity.

Aging↗
PubMed1991

Plasticity of neuroendocrine-immune interactions during aging.

Intact neuroendocrine-immune interactions are essential for the development and functional maintenance of both systems. Normal physiological aging appears to be, in part, dependent on age-related modifications of neuroendocrine-immune interactions. The thymus plays a major role in this context. Experimental manipulation at the thymic or neuroendocrine level may reciprocally correct the age-associated dysfunctions, suggesting the reversible nature of such phenomena.

Adaptation, Physiological↗