摘要:

Communication between the neuroendocrine and immune systems is crucial to host defence in both health and disease. Stress adversely interferes with the function of the immune system but the mechanism of such stress-induced immunosuppression is not well understood. Corticotropin-releasing hormone (CRH) is a 41-amino residue peptide which primarily stimulates ACTH secretion. In addition, CRH integrates a series of responses during the stress response. Over the last few years increasing evidence has suggested that CRH, the major stress-integrating peptide, may also directly modulate immune system function. Thus, recent data have demonstrated that CRH acts centrally as an immunosuppressant agent independent of circulating glucocorticoids. This central immunosuppressive effect of CRH is mediated at least partly via the central stimulation of sympathetic outflow. At a peripheral level, the presence of CRH and CRH receptors within cells of the immune system, and its complex effects directly on immune function, suggest that CRH is intimately associated with communication between the neuroendocrine and immune systems.

ISSN:1021-7401    

DOI:10.1159/000097184

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

It has recently been reported that both physical and psychological stress elevate plasma inter-leukin (IL)-6 levels independently of endotoxemia, tissue damage, or inflammation. However, the mechanism of plasma IL-6 elevation in these models is poorly understood. In the present study, plasma IL-6 levels were measured using the IL-6-dependent murine hybridoma subclone B9 cell line, which is commonly used by other investigators. We first demonstrated that an immobilization (IM) stress, a typical physicopsychological stress, increased plasma IL-6 levels. Then the contribution of the hypothalamic-pituitary-adrenal (HPA) axis and the central and peripheral catecholaminergic systems in IM-induced plasma IL-6 elevation were examined because these mechanisms play important roles in host defense against stress. Blood samples were collected through an indwelling jugular venous catheter before, during, and after IM; the number of samples taken serially from each animal was 12-13. Blood cells were resuspended in a saline solution and injected into the animals through the same catheter after each blood collection in order to prevent loss of blood volume. After initiation of restraint, plasma IL-6 levels significantly increased at 60 min and peaked at 90 min in the animals immobilized for either 30 or 120 min. The peak levels of IM-induced plasma IL-6 in the animals immobilized for 120 min (1,905 ± 414 U/ml) were significantly higher than those in the animals subjected to 30 min IM (837 ± 95 U/ml; p < 0.05). In the hypophysectomized (Hypox) or adrenalectomized (ADX) rats, the peak levels of IM-induced (60 min) plasma IL-6 were considerably higher than in sham-operated rats (Hypox: 33,281 ± 4,983 U/ml at 150 min; ADX: 52,020 ± 19,231 U/ml at 120 min). In addition, in order to determine the possible involvement of endogenous catecholamines in IM-induced plasma IL-6 elevation, 6-hydroxydopamine (6-OHDA) was injected into the lateral cerebral ventricle (i.cv., 100 µg/rat) or jugular vein (i.v., 100 mg/kg) of the rats, and the animals were exposed to IM stress 1 week (i.cv.) or 3 days (i.v.) after injection. Both i.cv. and i.v. injections of 6-OHDA markedly attenuated the plasma IL-6 response to IM as compared to the respective vehicle-injected group, whereas the plasma adrenocorticotropic hormone response to IM stress was reduced only by pretreatment with an i.cv. injection of 6-OHDA. These data suggest that (1) neither the pituitary nor the adrenal gland is a major source of increased plasma IL-6 induced by IM stress; (2) the HPA axis exhibits a suppressive regulatory role in the IM-induced IL-6 response; (3) both the central and peripheral catecholamines play critical roles in causing IL-6 elevation induced by IM stress, and (4) the involvement of peripheral catecholamines in elevating plasma IL-6 by IM stress is independent of HPA axis activation. Moreover, to determine whether splenocytes are the source of IM-induced plasma IL-6, splenectomized (Splex) rats were examined for their plasma IL-6 response to IM stress. The peak IL-6 levels after IM in Splex animals were significantly higher than those in sham-operated animals (p < 0.05). The immune-competent cells in the spleen, as well as the pituitary and adrenal glands do not seem to be a source of the increased levels of plasma IL-6 induced by IM st

ISSN:1021-7401    

DOI:10.1159/000097185

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

A monoclonal antibody (mAb), designated PS-11.2, was generated by immunizing mice with recombinant porcine growth hormone (pGH). This antibody recognized GHs of porcine, bovine (bGH) and chicken (cGH) origins, but not human GH, ovine prolactin, somatostatin S-14, and GH-releasing factor (1-29-NH2. Western analysis indicated that PS-11.2 predominantly identified not only the 22.5-kD protein but also its 45-kD dimer. It also recognized the 4.5- and 10-kD fragments of pGH resulting from trypsin digestion. The binding kinetics of PS-11.2 to pGH was determined by the biospeciflc interaction analysis in a real-time mode. The association and dissociation rate constants were estimated as 1.4 x 105M-1 s-1 and 2.2 x 10-4 s-1, respectively, thus producing an overall affinity of Kd = 1.6 x 10-9M. It partially inhibited the interaction of pGH and GH-binding protein in a competitive radioimmunoassay, suggesting that the pGH epitope recognized by PS-11.2 was closely related to the region responsible for engaging with GH receptors. Growth-deficient hypophysectomized rats were used for functional evaluation and shown to grow in response to the treatment of pGH. This effect was further augmented when pGH was administered together with PS-11.2, although antibody itself did not promote the growth of these animals. The antibody-mediated effect continued beyond the 5-day treatment period, indicating its long-lasting effect. Similar enhancement by PS-11.2 was also observed with bGH and cGH in this rat model. Therefore, the present findings clearly suggest that the somatogenesis of GH can be potentiated by PS-11.2 and that this mAb may serve as a useful tool for improving the growth performance of livestock.

ISSN:1021-7401    

DOI:10.1159/000097186

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The proinflammatory peptide substance P (SP) has been shown to be intimately involved in the local inflammatory processes ofTrichinella-spiralis-induced murine intestinal inflammation. Significant increases in SP, increased myeloperoxidase levels coupled with local morphological deterioration of the jejunum and impaired lymphocyte responses to exogenous SP in vitro have been associated with the model. We have recently determined that the elimination of increased levels of SP via anti-SP antibody therapy can spare the murine gastrointestinal tract much of the pathologies associated with the parasitic infection. Here we further demonstrate that the somatostatin analogue SMS 201 -995 as well as the SP receptor antagonist CP 96,345 can effectively decrease the inflammation and lost lymphocyte function seen in the jejunum ofT. spiralis-infected mice. Again, both intestinal morphology and myeloperoxidase levels were shown to return to normal values upon treatment. The above results suggest that SP is an important modulator of gastrointestinal inflammation.

ISSN:1021-7401    

DOI:10.1159/000097187

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We analyzed the effect of tumor necrosis factor α (TNF-α) on β-endorphin concentrations and proopiomelanocortin mRNA in the rat anterior and neurointermediate pituitaries. The intraperitoneal injection of 5 (µg/kg TNF-α decreases β-endorphin in neurointermediate pituicytes 4, 8 and 24 h after the treatment without affecting proopiomelanocortin (POMC) RNA. In contrast, in the anterior pituitary 4 h after the injection of the cytokine, POMC RNA was decreased while the peptide content was increased. These effects can be relevant to the modulation of the pituitary-adrenal axis and immune responses in conditions, such as infections, in which TNF levels are incr

ISSN:1021-7401    

DOI:10.1159/000097188

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The effects of interleukin-2 (IL-2) on various models of experimental epilepsy were studied after intracerebroventricular administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. Convulsions were induced by physical stimulus (sound of 109 dB, 12-16 kHz) or by chemical compounds (bicuculline, cephazolin or kainate). The present study demonstrated that human recombinant IL-2 (hr-IL-2) and mouse recombinant IL-2 (mr-IL-2) not only did not antagonize audiogenic seizures in DBA/2 mice but increased the incidence of seizures after the highest doses studied. In addition, hr-IL-2 and mr-IL-2 dose dependency facilitated sound-induced seizures at subthreshold sound exposure (8 3 dB). Pretreatment with monoclonal rat-anti-mouse IL-2 antibodies significantly affected the changes of occurrence of audiogenic seizures in DBA/2 mice induced by mr-IL-2. In addition, pretreatment with anti-IL-2 receptor monoclonal antibodies (anti-Tac) was able to completely antagonize or reduce the effects of IL-2 on audiogenic seizures. The effects of mr-IL-2 were also studied in two different models of epilepsy: the bicuculline and cephazolin models, due to impairment of GABAergic transmission, and the kainate model, due to an increase in excitatory amino acid transmission. In all models, mr-ILr2 demonstrated to facilitate the seizures induced by these chemoconvulsants. Since the proconvulsant properties of IL-2 were antagonized by specific monoclonal antibodies, we suggest that some epileptic phenomena may be linked to stimulation of IL-2 receptors. Further experiments will be necessary in order to ascertain whether IL-2 acts via the potentialization of the effects of excitatory amino acids or via inhibition of GABA activity, or both in the brain.

ISSN:1021-7401    

DOI:10.1159/000097189

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

It is believed that the expression of the conditioned natural killer cell activity is regulated through the hypothalamus-pituitary axis. Since the conditioned expression of both the plasma level of adrenocorticotropic hormone and natural killer (NK) cell activity show a sequential rise after exposure to the conditioned stimulus, it was of interest to determine if treatment with dexamethasone could inhibit this response. These studies suggest that treatment with dexamethasone was able to block the expression of the conditioned NK cell activity but was unable to interfere with the pairing of the conditioned stimulus with the unconditioned stimulus. We conclude that the hypothalamic pituitary axis is an integral part of the pathway for stimulation of NK cell activity in the spleen.

ISSN:1021-7401    

DOI:10.1159/000097190

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The effect of phorbol ester on the synthesis of nitric oxide (NO) in murine microglial cells was examined. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, alone had no effect, whereas PMA with recombinant interferon (rIFN)-γ synergistically increased NO synthesis in murine microglial cells. The maximal effect of PMA on NO synthesis increase always fitted with the range for full activation of PKC in these cells. The increase of NO synthesis was reflected as increased amount of immunologic NO synthase (iNOS) mRNA detected by Northern blotting. Treatment with PKC inhibitors such as staurosporine or polymyxin B decreased rlFN-γ-plus-PMA-stimuIated NO synthesis. Further, prolonged incubation of the cells with PMA, which down-regulates PKC activity, abolished the synergistic cooperative effect with IFN-γ. NG-monomethyl-L-arginine monohydrate, an analogue of L-arginine, and arginase inhibited rIFN-γ-plus-PMA-induced NO production in murine microglial cells. On the basis of these observations, we conclude that PKC might not be involved in the expression of iNOS, but instead, might be involved in the posttranscriptional modification of iNOS m

ISSN:1021-7401    

DOI:10.1159/000097191

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1021-7401    

DOI:10.1159/000097192

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1021-7401    

DOI:10.1159/000097193

出版商:S. Karger AG    

年代:1994

数据来源: Karger