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Biomedical subjects

W Pierpaoli

Publications and source records attributed to W Pierpaoli.

At least 37 records · Page 2Linked to original sources
PubMed1994

The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice.

It has been demonstrated that melatonin, the main neuro-hormone of the pineal gland, affects thymic functions and the regulation of the immune system. In addition, experimental evidences indicate that melatonin can modulate zinc turnover. The knowledge that with advancing age both melatonin and zinc plasma levels decline, and that zinc supplementation in old mice is able to restore the reduced immunological functions, has prompted investigations on the effect of chronic melatonin treatment or pineal graft in old mice on the age-related decline of thymic endocrine activity, peripheral immune functions and zinc turnover. Both melatonin treatment in old mice and pineal graft into the thymus of old mice correct the reduced thymic endocrine activity and increase the weight of the thymus and its cellularity. A restoration of cortical thymic volume, as detected by the percentage of tissue in active proliferation, is also observed in old mice after both treatments. Thymocyte CD phenotype expression is also restored to young values. At peripheral level, recovery of peripheral blood lymphocyte number and of spleen cell subsets, with increased mitogen responsiveness also occurs. Melatonin treatment or pineal graft induce also a restoration of the altered zinc turnover in aged mice with an increment of the crude zinc balance from negative (-1.6 microgram/day/mouse) to positive value (+1.2 microgram/day/mouse), similar to that one of young mice (+1.4 microgram/day/mouse). The reduced zinc plasma level is restored to normal values. These findings support the idea that the effect of melatonin on thymic endocrine activity and peripheral immune functions may be mediated by the zinc pool.

Aging↗
PubMed1993

Pineal grafting and melatonin induce immunocompetence in nude (athymic) mice.

The administration of melatonin to thymocyte-infused nude mice during the evening (dark cycle) of the circadian period restores transplantation immunity permanently, whereas inoculation during the morning cycle is quite ineffective. Transplantation of an intact pineal gland from normal donors into the mediastinal (athymic) tissue of nude mice leads to restoration of the capacity to reject skin grafts. Findings such as these attest to the genesis of transplantation immunity as linked to a thymus-directed establishment of a pineal circadian cyclicity.

Animals↗
PubMed1992

The involvement of pineal gland and melatonin in immunity and aging: II. Thyrotropin-releasing hormone and melatonin forestall involution and promote reconstitution of the thymus in anterior hypothalamic area (AHA)-lesioned mice.

A stereotactic electrolytic lesion of the anterior hypothalamic area in mice produces a rapid involution of the thymus and a reduction of lymphocytes in the peripheral blood. This effect on the thymus and blood lymphoid compartment can be prevented by postoperational administration of thyrotropin-releasing hormone (TRH) or melatonin. These activities of TRH or melatonin are antagonized by the opioid receptor blocker naltrexone. They do not seem to depend on stimulation of the thyroid gland or of the endogenous opioid system but rather on a direct activity of TRH on thymic targets or binding sites on lymphocytes.

Aging↗
PubMed1991

Iron carrier proteins facilitate engraftment of allogeneic bone marrow and enduring hemopoietic chimerism in the lethally irradiated host.

Cell-free supernatants of rabbit bone marrow were fractionated, separated, and purified by Ultrogel and Superose chromatography. A single fraction promoted engraftment of allogeneic bone marrow and enduring hemopoietic chimerism across the H-2 barrier in lethally irradiated mice. This "bio-active" fraction, analyzed by reducing SDS-PAGE electrophoresis, and transblotted on PVDF membrane, and purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main prealbumin band that when examined for primary structure by Edman degradation, proved to be rabbit transferrin. This was also attested by highly specific precipitation of the prealbumin band with polyclonal antibodies to rabbit transferrin. Iron-saturated human transferrin, lactotransferrin, and egg transferrin (conalbumin) were assayed in irradiated C57BL/6 mice infused with bone marrow from histoincompatible BALB/c donors. Mice treated with iron-loaded transferrins survive and develop enduring allogeneic chimerism with no discernible signs of graft-versus-host disease. Iron carrier proteins thus provide an unique means of achieving successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations.

Amino Acid Sequence↗
PubMed1990

The involvement of pineal gland and melatonin in immunity and aging. I. Thymus-mediated, immunoreconstituting and antiviral activity of thyrotropin-releasing hormone.

Circadian, continued treatment with melatonin during the dark cycle produces changes in the blood level of thyroid hormones in aging mice. Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) antagonize the involution of the thymus produced by prednisolone. This effect of TRH does not seem thyroid dependent. TRH restores antibody production in non-responder athymic nude mice but does not exert this effect in neonatally thymectomized mice. Moreover, this activity does not correlate with thyroxine levels. TRH exerts a powerful protective effect in mice challenged with encephalomyocarditis (EMC) virus. Presumably pineal melatonin exerts its varied regulatory functions via hypothalamic TRH.

Aging↗
PubMed1990

[The effect of iron carrier proteins on the transplantation of H-2 locus-incompatible bone marrow in irradiated mice].

Rabbit bone marrow supernatants were fractionated and purified by Ultrogel and Superose chromatography. A unique fraction promoted engraftment of allogenic bone marrow and enduring hemopoietic chimerism across the histocompatibility (H-2) barrier in lethally irradiated mice. This fraction analysed by reducing SDS-PAGE electrophoresis and transblotted on PVDF membrane or purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main pre-albumin band that was examined for primary structure by Edman degradation. It appeared to be rabbit transferrin. Iron saturated human transferrin, lactotransferrin and egg transferrin (conalbumin) were then tested in irradiated C57B1/6 mice transplanted with bone marrow from histoincompatible BALB/CJ donors. Most mice treated with iron-loaded transferrins survived and developed enduring allogeneic chimerism with no discernible signs of graft-versus-host disease at 10 months posttransplant. Observation of these animals is still carried on. Iron carrier proteins seem to provide a novel unexpected means for achieving a successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations and may open a new approach in the clinical area.

Animals↗
PubMed1988

Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism.

We have recently demonstrated that the pineal neurohormone melatonin exerts important immunoregulatory functions. We now report that exogenous melatonin counteracts completely the effect of acute anxiety-restraint stress on thymus weight and antibody response to sheep red blood cells (SRBC). In addition, administration of melatonin in the evening prevented paralysis and death of mice infected with sublethal doses of encephalomyocarditis virus (EMCV) after acute stress. The anti-stress activity of melatonin was present in mice injected with T-dependent antigens, and it was abolished by the contemporary administration of the specific opioid-antagonist naltrexone. This suggests that melatonin exerts its remarkable anti-stress effect on antigen-activated cells via an opiatergic mechanism. These findings have important implications at both basic and clinical levels. They provide a new approach to a possible physiological 'up-regulation' of the immune response under virus- and/or stress-related immunosuppression.

Acute Disease↗
PubMed1987

Melatonin: a principal neuroimmunoregulatory and anti-stress hormone: its anti-aging effects.

Major environmental variables such as daily and seasonal changes of light and temperature regulate the daily circadian variations of synthesis and release of the pineal neurohormone N-acetyl-5-methoxytryptamine (melatonin). Melatonin has now been shown to be a potent immunoregulatory agent, and to be able to antagonize the immunosuppressive effects of acute anxiety stress in mice, as measured by antibody production, by thymus weight, and by the capacity of stressed- and evening-melatonin-treated mice to react against a lethal virus. Both psychogenic factors and infectious agents such as viruses can act as "stressors" and induce an immunosuppression. Their combination is a determinant for the course of infectious diseases and, perhaps, cancer. Circadian (evening) melatonin possesses thus the singular ability to up-regulate the immunosuppression of stressed mice. This effect of melatonin is not exerted directly on immunocompetent cells, but mediated via the endogenous opioid system upon antigen-activation of T cells. Melatonin being a short-lived hormone with negligible side-effects which is rapidly degraded and eliminated by the body, the use of melatonin offers a new approach to the physiological control of stress and stress-related infectious diseases. In addition, melatonin could be used for the potentiation of primary immunization (vaccination) against antigens of the most varied nature which do not evoke a robust or longlasting secondary (memory) response. The regulatory function of pineal melatonin is discussed also in relation to hematopoiesis, to its oncostatic effects, and to its possible dual role in reproduction physiology and generation of immunocompetence and tolerance during ontogeny.

Aging↗
PubMed1987

Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism.

The pineal gland constitutes a major neuroendocrine organ in the brain. It transduces exogenous signals such as circadian and seasonal variations of light and temperature into proper hormonal changes which adjust and adapt internal endocrine functions. These pineal activities seem to be exerted via circadian synthesis and release of the indoleamine melatonin, a neurohormone secreted by the pineal itself. Alteration of circadian rhythms have been associated with affective disorders, psychosomatic diseases, cancer and many other pathologies. We have reported that functional and pharmacologic inhibition of melatonin synthesis results in depressed immune functions in vivo and that exogenous, evening administration of melatonin enhances antibody formation via an antigen-activated process and also antagonizes the immunosuppressive effects of corticosterone. We communicate here findings demonstrating that (a) three different inbred strains of mice possess a clear-cut cycle of melatonin levels in serum, (b) that melatonin administered in the evening enhances primary antibody response (IgM and IgG immunoglobulins) in vivo according to a dose-response behaviour and that (c) the opioid receptors blocker naltrexone antagonizes the immunostimulatory effect of melatonin. These findings point to a fundamental immunoregulatory role of circadian melatonin and to an activity of the neurohormone via opioid peptides.

Animals↗