摘要:

The autonomic innervation of the lymphoid tissue is currently visualized as a channel for neural regulation of immunity. Several reports have dealt with the alteration of antibody responses of spleen and lymph nodes following sympathectomy, and less often, parasympa-thectomy. This article reviwes published data on the local effects of sympathetic and parasympathetic neurons innervating immunocompetent organs on immune responsiveness. A model comprising bilateral lymphoid organs (the submaxillary lymph nodes) and the local ipsilateral manipulation of their regional sympathetic nerves (derived from the superior cervical ganglia) and of their regional parasympathetic nerves (conveyed through the lingual nerve-chorda tympani) allowed the description of purely local effects of the autonomic nerves independent of the systemic effects of the surgical manipulation itself. By employing this model, the following were observed. (1) After the unilateral sympathetic denervation of murine submaxillary lymph nodes by superior cervical ganglionectomy (SCGx), ipsilateral increases in plate-forming cell (PFC) activity, delayed hypersensitivity and graft-versus-host reactions were observed as compared to the contralateral, sham-operated, submaxillary lymph nodes. During degeneration of peripheral sympathetic nerves shortly after SCGx, PFC activity in ipsilateral submaxillary lymph nodes decreased significantly. (2) The local parasympathetic decentralization of murine submaxillary lymph nodes, achieved by the unilateral section of the chorda tympani, resulted in decreases of PFC activity, when challenged 10-20 days after denervation. (3) In the course of the immune reaction induced by the injection of complete Freund's adjuvant in rats, an augmented activity of local autonomic nerves was found in the submaxillary lymph nodes, as shown by the increase of neuronal norepinephrine uptake and tyrosine hydroxylase activity (two markers of noradrenergic activity), and of neuronal choline uptake and choline acetyltransferase activity (two markers of cholinergic activity). (4) Coincident with the augmented immune response after local sympathetic denervation of submaxillary lymph nodes, the growth of transplanted tumors in the cutaneous territory was significantly impaired in rats. (5) In the absence of an intact local sympathetic innervation, the effect of the immunosuppressive drug cyclosporine in rat submaxillary lymph nodes [as assessed by the inhibition of ornithine decarboxylase (ODQ induction after complete Freund's adjuvant injection] became significantly attenuated. (6) A similar impairment of cyclosporine activity on submaxillary lymph node ODC was found in Freund's-adjuvant-treated rats subjected to a regional unilateral parasympathetic decentralization by chorda tympani section 2 weeks later. (7) In rats injected with either Freund's adjuvant or its vehicle, the sympathetic denervation of submaxillary lymph nodes by unilateral SCGx augmented the stimulatory activity of cyclosporine on choline acetyltransferase and neuronal choline uptake. The results indicate that an appropriate sympathetic and parasympathetic local environment is needed for normal immune responsiveness and immunomodu-lation.

ISSN:1021-7401    

DOI:10.1159/000097175

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The autonomic innervation of the lymphoid tissue is currently visualized as a channel for neural regulation of immunity. Several reports have dealt with the alteration of antibody responses of spleen and lymph nodes following sympathectomy, and less often, parasympa-thectomy. This article reviwes published data on the local effects of sympathetic and parasympathetic neurons innervating immunocompetent organs on immune responsiveness. A model comprising bilateral lymphoid organs (the submaxillary lymph nodes) and the local ipsilateral manipulation of their regional sympathetic nerves (derived from the superior cervical ganglia) and of their regional parasympathetic nerves (conveyed through the lingual nerve-chorda tympani) allowed the description of purely local effects of the autonomic nerves independent of the systemic effects of the surgical manipulation itself. By employing this model, the following were observed. (1) After the unilateral sympathetic denervation of murine submaxillary lymph nodes by superior cervical ganglionectomy (SCGx), ipsilateral increases in plate-forming cell (PFC) activity, delayed hypersensitivity and graft-versus-host reactions were observed as compared to the contralateral, sham-operated, submaxillary lymph nodes. During degeneration of peripheral sympathetic nerves shortly after SCGx, PFC activity in ipsilateral submaxillary lymph nodes decreased significantly. (2) The local parasympathetic decentralization of murine submaxillary lymph nodes, achieved by the unilateral section of the chorda tympani, resulted in decreases of PFC activity, when challenged 10-20 days after denervation. (3) In the course of the immune reaction induced by the injection of complete Freund's adjuvant in rats, an augmented activity of local autonomic nerves was found in the submaxillary lymph nodes, as shown by the increase of neuronal norepinephrine uptake and tyrosine hydroxylase activity (two markers of noradrenergic activity), and of neuronal choline uptake and choline acetyltransferase activity (two markers of cholinergic activity). (4) Coincident with the augmented immune response after local sympathetic denervation of submaxillary lymph nodes, the growth of transplanted tumors in the cutaneous territory was significantly impaired in rats. (5) In the absence of an intact local sympathetic innervation, the effect of the immunosuppressive drug cyclosporine in rat submaxillary lymph nodes [as assessed by the inhibition of ornithine decarboxylase (ODQ induction after complete Freund's adjuvant injection] became significantly attenuated. (6) A similar impairment of cyclosporine activity on submaxillary lymph node ODC was found in Freund's-adjuvant-treated rats subjected to a regional unilateral parasympathetic decentralization by chorda tympani section 2 weeks later. (7) In rats injected with either Freund's adjuvant or its vehicle, the sympathetic denervation of submaxillary lymph nodes by unilateral SCGx augmented the stimulatory activity of cyclosporine on choline acetyltransferase and neuronal choline uptake. The results indicate that an appropriate sympathetic and parasympathetic local environment is needed for normal immune responsiveness and immunomodu-lation.

ISSN:1021-7401    

DOI:10.1159/000315052

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The type I glucocorticoid receptor antagonist spironolactone was administered to healthy volunteers to determine the effect of type I receptor blockade on adrenocorticotropic hormone (ACTH) and Cortisol secretion in humans. On separate days and in a double-blind, randomized fashion, placebo and each of four increasing doses of spironolactone were administered orally to subjects. Doses were selected to be within the clinically used range and, following drug administration, baseline and ovine-corticotropin releasing hormone (oCRH)-stimulated ACTH and Cortisol plasma levels were measured. In contrast to the clear effects of type II glucocorticoid receptor blockade on human pituitary adrenal function, no relationship between spironolactone dose or plasma levels and either basal or oCRH-stimulated pituitary-adrenal function was noted at doses comparable to those which induce type I receptor blockade and cardiovascular therapeutic effects in the kidney. These data suggest that, at physiologically relevant doses, type I glucocorticoid receptor blockade does not affect HPA axis function.

ISSN:1021-7401    

DOI:10.1159/000097176

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In the present study, lidocaine, a local anesthetic that inhibits the initiation or conduction of nerve impulses, was used to differentiate between the memory for the conditioned stimulus (CS) and the memory for the CS and unconditioned stimulus (US) association. Lidocaine was used to block memory formation. It was administered into the cisterna magna to localize the inhibition to the central nervous system (CNS) where circuits for the CS and US exist. The results show that lidocaine specifically blocks the ability of the CS to stimulate the circuits responsible for storing the CS/US association, but it does not interfere with the inherent aof the US to signal the CNS and trigger a peripheral response. The observation that the CS circuit can be interrupted independently of the US circuit suggests that these signals come together to form a new circuit for the memory of the association. The association memory forms later and is independent of the memory for the CS.

ISSN:1021-7401    

DOI:10.1159/000097177

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The possible role of altered humoral immunity in cardiac Chagas'' disease was examined by analyzing the interaction of IgG and the corresponding F(ab′)2 from Trypanosoma cruzi-infected patients with cardiac muscarinic cholinergic receptors (mAchR). Human chagasic IgG and its F(ab′)2 simulated the agonist amons triggering the biological effects associated with cholinergic-mediated cellular transmembrane signals, i.e. stimulation of cGMP, inhibition of cAMP and a decrease in atrial contractility. Atropine blunted all of these effects while pertussis toxin prevented the inhibition of cAMP and contractility confirming the G-regulatory-protein-mediated response in the interaction of chagasic antibodies with cardiac mAchR. In addition, chagasic IgG and its F(ab′)2 behaved as partial agonists activating the specific receptor and inhibiting in a noncompetitive manner the activity of an exogenous agonist (pilocarpine). Moreover, chagasic IgG immunoprecipitated the mAchR solu-bilized from cardiac membrane in a concentration-dependent fashion. By means of SDS-PAGE and immunoblotting analysis, chagasic serum was shown to recognize a band of approximately 75 kD. The electrophoretic studies of prelabeled immunoprecipitated proteins revealed a peak of [3H] propyl-benzilylcholine mustard with an apparent molecular weight similar to that of mAchR, which disappeared in the presence of atropine. The presence of these antibodies in the serum of chagasic patients could explain the progressive receptor blockade in the parasympathetic branch of the cardiac autonomic nervous system associated with the cardioneuromyopathy described in the course of Chagas'' di

ISSN:1021-7401    

DOI:10.1159/000097178

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

To explore the interaction between the hypothalamic-pituitary-adrenocortical axis and the immune system under stress conditions, we used an experimental rat model for chronic tail-restraint devise earlier for ground studies in space physiology. The system was used in two positions: (1) the orthostatic restraint position (OR) and (2) the antiorthostatic position (AOR) after the rat hind limbs had been raised by a head-down tilt. After 7 days of either restraints sequential blood samples were taken via an indwelling aortic cannula, before and at various time intervals between 15 and 300 min after an intravascular infusion of 25 µg/kg lipopolysaccharide (LPS). The plasma titers of adrenocorticotropin (ACTH), corticosterone (CORT) and interleukin-1β (IL-1β) were assayed. Under basal conditions, both OR and AOR restraints induced a 5-fold increase in IL-1β with no significant changes in ACTH and CORT levels. A robust increase in all three variables was observed after LPS injection. However, the IL-1β response to LPS was significantly higher in both restrained groups than in controls. Both the amplitude and the percentage of individually restrained rats displaying elevated IL-1β levels were increased up to 5 h. In contrast, the ACTH and CORT post-LPS responses were normal in the OR group. They were unusually dissociated in the AOR rats, which displayed depressed ACTH levels associated with slightly increased CORT levels. Our results suggest that immune-neuroendocrine responses to chronic restraint stress may differ from those generally observed in acute s

ISSN:1021-7401    

DOI:10.1159/000097179

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In experimental animals and humans, bacterial endotoxin activates the hypo-thalamus-pituitary-adrenal (HPA) axis. The pathways by which endotoxin stimulates adrenocorticotropic hormone (ACTH) and corticosterone secretion are uncertain. In the present study we compared the role of hypothalamic corticotropin-releasing hormone (CRH) in the activation of the HPA axis by a low (2.5 µg/kg) and a high (2.5 mg/kg) dose of bacterial endotoxin. Two experimental models were applied using chronically cannulated male Wistar rats. In the first model, rats were subjected to lesions of the hypothalamus that interrupted dorsal, lateral and frontal input to the median eminence (anterolateral deafferentation) or to sham operation and rats were used 7 days later. Before and at hourly intervals after endotoxin (2.5 µg/kg i.p.), blood samples were taken for the determination of plasma ACTH and corticosterone concentrations. Deafferentation of the hypothalamus strongly attenuated the elevations in plasma ACTH and corticosterone concentrations by a low dose of endotoxin compared to the responses in sham-operated animals. The second model involved passive immunization to CRH using a monoclonal antibody to rat/human CRH (PFU83). PFU83 (90 nmol/rat) abolished the elevation of plasma ACTH concentrations and attenuated corticosterone responses to a low dose of endotoxin (2.5 µg/kg i.p.) compared to that in control IgG-treated rats. Since the corticosterone responses to endotoxin were less effectively inhibited by the antibody than the ACTH responses, we postulate that non-ACTH-dependent mechanisms may contribute to the corticosterone response to endotoxin. The same dose of PFU83 attenuated the endotoxin-induced ACTH responses to a high dose of endotoxin (2.5 mg/kg i.p.) by ± 45% but did not affect plasma corticosterone concentrations. We conclude that the ACTH responses to a low dose of endotoxin in rats are completely mediated by secretion of CRH from hypothalamic CRH-producing neurons that project to the median eminence, whereas the ACTH response induced by high doses of endotoxin is only partially dependent on

ISSN:1021-7401    

DOI:10.1159/000097180

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Treatment of neonatal rats with capsaicin causes a 92.4% loss of calcitonin-gene-related-peptide-immunoreactive unmyelinated sensory afferent fibres in the airways epithelium, vascular smooth muscle and perivascular adventitial layer of lung tissue compared with vehicle-treated controls. Rats were administered Sephadex particles i.v. 8–10 weeks after either capsaicin or vehicle treatment at birth in order to induce a granulomatous tissue inflammation, peripheral blood eosinophilia and pulmonary eosinophil invasion [Laycock et al., Int Arch Allergy Appl Immunol 1986;81:363-367]. The animals also exhibited lung hyperreactivity in vitro in response to carbachol and serotonin (5HT). In Sephadex-treated rats, capsaicin pretreatment did not affect the number of inflammatory cells in peripheral blood, the number of eosinophils in lung tissue, or the distribution of eosinophils in the adventitial tissue of blood vessels. Potencies of concentration-related contractures of lung tissue to 5HT and carbachol were increased by 50- to 100-fold in Sephadex-treated animals compared to controls, but in neither group was potency influenced by capsaicin pretreatment at birth. Recruitment and subsequent regional distribution of inflammatory cells in lung tissue and the increase in lung hyperresponsiveness exhibited in this model of asthma do not appear to involve neuropeptides released from primary afferent neurone

ISSN:1021-7401    

DOI:10.1159/000097181

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Many studies have documented the presence of a sexually dimorphic response of neuroendocrine functions in response to immune signals. The aims of the present study were to evaluate the hypothalamopituitary-adrenal (HPA) axis response to inflammatory gross stimulus in 15-month-old mice, and to determine whether such a response depends on circulating sex steroids. Our results indicate that in the 15-month-old mice: (1) there is a sexual dimorphism in the HPA axis activity in basal condition and after endotoxin treatment with generally higher levels of several parameters of this axis in female than in male mice, (2) gonadectomy alone, followed by sex steroid therapy, modulates HPA axis function in both basal and stress conditions, and (3) whereas estradiol plays a stimulatory role on adrenal function, testosterone inhibits adrenal glucocorticoid production. This study further suggests a clear sexual dimorphism in middle-aged mice injected with endotoxin These results may be relevant for the treatment of sepsis in aged patients.

ISSN:1021-7401    

DOI:10.1159/000097182

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The aim of this study was to determine if the anticytokine neuropeptide α-melanocyte-stimulating hormone (α-MSH) occurs, along with interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFr), in synovial fluid of patients with rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), or osteoarthritis. The data show that α-MSH does occur in the synovial fluid and its concentrations are greater in patients with RA than in those with osteoarthritis. Synovial fluid concentrations of IL-1ra and sTNFr were likewise greater in RA. Further, concentrations of α-MSH, IL-1ra, and sTNFr were greater in patients with polyarticular/systemic-onset JCA than in those with pauciarticular disease, that is in patients with greater joint inflammation. Concentrations of α-MSH were greater in synovial fluid than in plasma in a substantial proportion of patients, suggesting local production of the peptide; this is the first indication that the anticytokine molecule α-MSH is produced within a site of inflammation. Further, it appears that local production of α-MSH is induced particularly in those arthritic joints that have more intense inflammatory reactions. This finding, combined with previous evidence of the marked anti-inflammatory activity of α-MSH, suggests that the peptide acts locally to modulate proinflammatory influences in rheumatic d

ISSN:1021-7401    

DOI:10.1159/000097183

出版商:S. Karger AG    

年代:1994

数据来源: Karger