摘要:

An anterior pituitary was grafted into the breast muscles of male rats on day 5, or under the kidney capsule on day 30 or 60 of life. At the 70th day of life (rats operated at the 5th or 30th day) or at the 100th day of life (rats operated at the 60th day), rats were injected subcuta-neously with Freund''s complete adjuvant, being killed 2 days later. Rats pituitary-grafted at the 30th day showed a greater hyperprolactinemia than rats grafted at the 5th or 60th day. Submaxillary lymph node natural killer (NK) activity decreased in neonatally pituitary-grafted rats and increased in rats grafted at the 30th or 60th day of life, while lymph node cellularity decreased in rats grafted at the 30th or 60th day. In the case of lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation in lymph nodes, the only significant factor detected was age of transplantation, the effect being less evident in older animals. To examine whether the autonomic denervation of submaxillary lymph nodes affected immune responses in pituitary-grafted rats, animals were subjected to a unilateral superior cervical ganglionectomy (Gx) and/or a parasympathetic decentralization (Dc; by chorda tym-pani section), 10 days before immunization with Freund''s adjuvant. A unilateral Gx blunted the stimulation of lymph node NK activity in rats receiving a pituitary transplant at the 30th or 60th day, but not at the 5th day. Only in sympathetically denervated lymph nodes a significant effect of pituitary transplants on LPS mitogenic effect was found, with significantly less effect of LPS in rats pituitary-grafted at the 5th or 30th day of life. Regarding Con A, a unilateral Gx or unilateral Gx plus Dc uncovered a significant depressive effect of pituitary transplants with a significantly smaller Con A mitogenic effect at each studied age in ipsilaterally Gx lymph nodes, and at 30 and 60 days of age in ipsilateraly Gx plus Dc lymph nodes. Pituitary grafts augmented Con A- induced proliferation in submaxillary lymph nodes at the 5th day of life while they decreased it at the 60th day of life. Pituitary transplants augmented cellularity at the sympathetically denervated lymph nodes and decreased it at the contralateral sham-operated side. Pituitary transplants also diminished lymph node cellularity at the Dc side, the effect being significant in rats transplanted at the 30th day of life. The results are compatible with age-dependent, inhibitory as well as promoting activities of hyperprolactinemia on immune responses in submaxillary lymph nodes, depending in part on intact autonomic nerves.

ISSN:1021-7401    

DOI:10.1159/000097309

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The cytokine interleukin-1 (IL-1) can act within the brain to induce peripheral endocrine and immune effects. In the rodent intracerebroventricular (i.c.v.) injection of IL-1 activates the hypothalamic-pituitary-adrenal axis and suppresses peripheral immune function by a CRH-dependent mechanism. It is unknown if IL-1 can similarly act within the brain to cause peripheral immunosuppression in the primate and to what extent this could be attributed to the IL-1-induced increase in ACTH and Cortisol levels. In this study we have characterized the pituitary-adrenal and peripheral lymphocyte responses to IL-1α(4.2µg) infused over 30 min into the lateral ventricle of ovariectomized monkeys (n = 5) as compared with responses to an intravenous (i.v.) ACTH infusion (1µg/h for 7 h; n = 4). Four serial blood samples were obtained for ACTH and Cortisol determination and for lymphocyte isolation during a 1-hour baseline and for 7 h after IL-1 or ACTH. Lymphocyte proliferation was measured by3H-thymidine uptake in response to stimulation with phytohemagglutinin. In all 5 animals, IL-1αcaused rapid and profound suppression of lymphocyte mitogen responsiveness for 7 h. Baseline lymphocyte proliferation was 51,800±9,780 cpm and suppressed to a nadir of 4.5% with a mean of 23% baseline over 7 h (p < 0.001). Mean ACTH and Cortisol levels increased from 33±(SEM) 4.6 pg/ml and 43±4.0µg/dl, respectively, during the control period to 90±14 pg/ml and 56±2.6µg/dl, respectively, after IL-1 (p < 0.01). Before i.v. ACTH, baseline lymphocyte proliferation was 49,400±2,820 cpm, and suppressed to a mean of 64% of baseline during ACTH infusion (p < 0.05). Mean ACTH and Cortisol levels increased from 48±5.0 pg/ml and 43±2.0µg/dl, respectively, to 170±34 pg/ml and 66±2.3µg/dl, respectively, during the ACTH infusion (p < 0.01). Lymphocyte suppression after i.c.v. IL-1 was much more profound than after i.v. ACTH (p < 0.01); the area under the IL-1 response curve was 37% of the area under the ACTH response curve. These studies demonstrate for the first time in the primate that centrally injected EL-1 has a profound suppressive effect on lymphocyte function. They also show for the first time in any species that there appears to be a significant immunosuppressive message produced by i.c.v. IL-1 that is not accounted for by the associated increases in

ISSN:1021-7401    

DOI:10.1159/000097310

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Several reports support the view that growth hormone (GH) promotes proliferation and cytotoxicity by T cells in a mixed leukocyte culture (MLC). The present study was undertaken to begin to determine the mechanism of action of GH on the MLC in vitro. First, we determined that peripheral blood mononuclear cells (PBMC) cultured with mitomycin-treated allogeneic PBMC in an MLC in the presence of exogenously added rhGH develop an augmented proliferative (25–100%) and cytotoxic response (50–600%). We next examined the possibility that GH may promote alloresponses by inducingγ-interferon (IFNγ) production. In these experiments, in situ hybridization was used to determine the frequency of cells expressing mRNA for IFNγ. It was observed that GH increased significantly the frequency of cells expressing mRNA for IFNγ(100-800%). To determine the site of action of rhGH, we evaluated the response of purified T cells to alloantigens in the presence of rhGH. The addition of rhGH to an MLC had no demonstrable effect when purified T cells were used as the responding population. However, when T cells were reconstituted with autologous mitomycin-treated PBMC and used as the responding population, rhGH augmented proliferation and cytotoxicity. Taken together, these data show that rhGH augments proliferation, cytotoxicity and IFNγproduction during an MLC, and at least part of the action of rhGH appears to be on the autologous antigen-present

ISSN:1021-7401    

DOI:10.1159/000097311

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Hemorrhage is associated with an impairment in the immune response and with increased concentrations of circulating inflammatory cytokines. The present study determined the time course and localization of alterations in circulating and tissue pro-inflammatory cytokines (TNF-α, IL-1-α and -β) in response to fixed-pressure (40 mm Hg) hemorrhage as well as the associated hanges in circulating neurohormonal and opioid mediators. Conscious unrestrained non-heparinized male Sprague-Dawley rats (n = 24) underwent hemorrhage followed by standard resuscitation with lactated Ringer''s solution. Animals were sacrificed at three time points; immediately after the hemorrhage period, at completion of resuscitation and 1.5 h after the resuscitation period. Hemorrhage resulted in marked elevations in circulating levels of TNF-α, which averaged 860 ± 201 pg/ml. The levels were similarly elevated following fluid resuscitation (877 ±196 pg/ml) and had decreased towards baseline 1.5 h after completion of resuscitation (281 ±134 pg/ml). TNF-α was not detectable in plasma of time-matched controls. Hemorrhage elevated TNF-α content in spleen (25%), lung (55%) and heart (20%), and tissue content remained elevated despite resuscitation. No significant changes in tissue content of TNF-α were detected in the liver, kidney or brain. Circulating levels of IL1-α and -β were not detectable in either the time-matched controls or hemorrhaged animals. However, statistically significant elevations in tissue content of IL-1α were observed in heart, spleen, lung, gut and whole brain (15–30%). Tissue content of IL-1β did not change in response to hemorrhage and/or fluid resuscitation. Activation of sympathetic outflow, as evidenced by a 3- to 4-fold elevation in circulating epinephrine and norepinephrine levels, was observed immediately after hemorrhage, and was associated with a 5-fold rise in circulating β-endorphin. These results demonstrate an early increase in tissue cytokine content following hemorrhagic shock, which is associated with elevations in circulating catecholamines and endogenous opioids, consistent with their potential modulatory role

ISSN:1021-7401    

DOI:10.1159/000097312

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The proinflammatory cytokine tumor necrosis factor-α(TNF-α) occurs in CNS tissue in neurological disorders, infection, and injury. Its excessive production is believed to contribute to local pathology, in which case modulation of TNF-αproduction should promote survival of neural tissue. The neuropeptideα-melanocyte stimulating hormone [α-MSH (1-13)] inhibits TNF-αproduction in vivo and in vitro, and in this research we tested the capacity of the peptide, and of an anti-inflammatory COOH-terminal tripeptide fragment of it, to inhibit TNF-αproduction induced by bacterial endotoxin in cells of a human glioma line (A-172, anaplastic astrocytoma cells). Both peptides were effective, although theα-MSH (1–13) sequence was more potent. Preincubation of the cells withα-MSH (1–13) markedly increased its effectiveness. The anticytokine effect ofα-MSH in glioma cells may be mediated by human melanocortin-1 receptors; mRNA for this receptor subtype was isolated from resting A-l 72 cells. These results, combined with prior evidence of effectiveness ofα-MSH molecules in modulating inflammatory processes and of their low toxicity, suggest that the molecules may be useful in the treatment of CNS disorders that have an inflamma

ISSN:1021-7401    

DOI:10.1159/000097313

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Peripheral blood concentrations of the proinflammatory peptide substance P (SP) have been shown to increase in response to psychological anxiety in human subjects. In this study, we examined changes in SP levels in peripheral blood in response to the anxiety of a diagnostic medical procedure. The levels of SP were found to be higher in subjects with high initial anxiety as compared to subjects with low initial anxiety as measured on the Multiple Affect Adjective Checklist. Changes in the percentages of CD-8-expressing T lymphocytes were found to correlate with alterations in measures of anxiety as well as SP. These changes persisted for 3 days following the diagnostic procedure. The results of the study seem to indicate that SP may serve as a mediator in stress-induced immune reactions.

ISSN:1021-7401    

DOI:10.1159/000097314

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The occurrence of brain tumors is associated with broad suppression of the immune system function; however, the mechanisms involved in this impairment are not fully characterized. In this study, we have examined mechanisms involved in diminished T lymphocyte reactivity in patients with glioblastomas as compared to patients with other types of brain tumors. We found that the proliferative response of T lymphocytes stimulated with phytohemagglutinin or anti-CD3 was significantly reduced in these patients as compared to patients with meningiomas, oligodendrogliomas and healthy individuals. Stimulated T cells appear to express lower levels of theα-subunit (p55) of the IL-2 receptor (IL-2R), and increased levels of soluble IL-2R in cell supernatants, whereas no significant differences were observed in the level of the β (p75)- orγ-subunits. In addition, we found that competent T cells of glioblastoma patients exhibit lower levels of tyrosine phosphorylation in response to IL-2 as compared with cells of healthy donors. The decrease in the levels of IL-2 and its receptor was selective since no significant changes were observed in the secretion of other Th1- and Th2-derived cytokines (IFN-γand IL-4) and the expression of their respective receptors. These results indicate that the diminished response of T cells obtained from patients with glioblastomas may be due to a selective defect in the production of IL-2 and in the expression of functional IL-2R due to a decreased expression of the membranal IL-2Rαand to lower levels of tyrosine phosphorylation in response to

ISSN:1021-7401    

DOI:10.1159/000097315

出版商:S. Karger AG    

年代:1997

数据来源: Karger