No abstract available.
Neuroimmunomodulation*

The nervous system and the immune system are relatively independent but interactional, and neuro-immune regulation is very important for the respiratory system to resist external harmful stimuli and to maintain homeostasis. Neuro-immune interaction is involved in the occurrence and development of respiratory diseases, and is essential for monitoring and modulating inflammation and tissue repair. This article summaries the neuro-immune regulation of respiratory system and discusses its role in respiratory diseases, aiming to provide a theoretical basis for further understanding the crosstalk between the nervous and immune systems, to explore the underlying mechanism in respiratory diseases, and to provide new thoughts for the prevention and treatment of respiratory diseases.
Homeostasis ; Humans ; Immune System ; Inflammation ; Nervous System ; Neuroimmunomodulation ; Respiration Disorders

The modern studies indicate that there is a close relationship between mast cells and the acupuncture effect, and acupuncture can activate mast cells to induce a series of vascular reaction and immunological effect. The authors hold that acupuncture is a kind of nociceptive stimulus, which can cause inflammatory reaction in the sites of acupuncture, and then further activate the nerve-endocrine-immune network to cause the cascade amplification of the acupuncture effect. The inflammatory reaction induced by acupuncture is one of the initial factors of acupuncture effect.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Humans ; Immunity ; Mast Cells ; immunology ; Nerve Fibers ; immunology ; Neuroimmunomodulation ; Skin ; immunology

The cholinergic anti-inflammatory pathway (CAP) is a neuro-immunomodulatory pathway,in which acetylcholine (ACh) released by the interaction of vagal nerves with α7 nicotinic acetylcholine receptor (α7nAChR),which prevents the synthesis and release of pro-inflammatory cytokines and ultimately regulates the local or systemic inflammatory response in a feedback manner. It has been shown that there are many possible effective treatments for sepsis, including vagus nerve stimulation by physical therapy, drugs such as acetylcholine receptor agonist and ultrasound therapy.
Acetylcholine ; Humans ; Inflammation ; Neuroimmunomodulation ; Sepsis ; Vagus Nerve Stimulation ; alpha7 Nicotinic Acetylcholine Receptor

OBJECTIVE: To investigate the role of cholinergic anti-inflammatory pathway (CAP) in neuro-regulation of inflammatory and immune response in the early stage of sepsis. METHODS: Sixty-four SD rats were randomly divided into control Group (=8) with normal feeding without any treatment; sham operation group (=8) with laparotomy but without cecal ligation and puncture (CLP), followed by intraperitoneal injection 50 mg/kg piperacillin 3 times a day for 3 consecutive days; and sepsis group (=48) with CLP-induced sepsis. The rat models of sepsis were randomized into model groups (=16) with intraperitoneal injection of piperacillin (50 mg/kg) and normal saline (1 mL/100 g) for 3 times a day for 3 days; GTS-21 group (=16) with additional intraperitoneal injection of 4 mg/kg GTS-21 (once a day for 3 days); and methyllycaconitine (MLA) group (=16) with intraperitoneal injection of MLA (4.8 mg/kg) in addition to piperacillin (once a day for 3 days). Murine Sepsis Score (MSS) of the rats and short-range HRV analysis were recorded. Three days later, the rats were sacrificed and serum levels of TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 were measured with ELISA. The percentages of CD4CD25 Treg and TH17 lymphocytes and their ratios were measured using flow cytometry. RESULTS: Compared with the control rats, the septic rats had significantly increased MSS scores and lowered HRV indexes (SDNN, RMSSD, HF, SD1, and SD2; < 0.05); treatment with GTS-21 significantly decreased while MLA increased MSS scores ( < 0.05), but neither of them obviously affected HRV of the rats. Serum levels TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 and the percentages of CD4CD25 Treg and TH17-positive lymphocytes were significantly higher and Treg/TH17 ratio was significantly lower in the septic rats compared with those in the control group ( < 0.05); treatment with GTS-21 significantly decreased the levels of serum levels of TNF-α, IL-1α, IL-6, HMGB1, and sCD14 and TH17 lymphocyte percentage ( < 0.05), whereas MLA treatment significantly increased serum levels of TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 and the percentages of CD4 CD25 Treg and TH17-positive lymphocytes and decreased Treg/TH17 ratio in the septic rats ( < 0.05). CONCLUSIONS CAP plays negative regulatory role in early inflammatory and immune response to sepsis, and some of the HRV indicators can well reflect the regulatory effect of CAP on inflammation and immunity in the septic rats.
Animals ; Disease Models, Animal ; Mice ; Neuroimmunomodulation ; Rats ; Rats, Sprague-Dawley ; Sepsis ; T-Lymphocytes, Regulatory

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is an acute monophasic paralytic central nervous system disease, in which most rats spontaneously recover from paralysis. EAE in Lewis rats is induced by encephalitogenic antigens, including myelin basic protein. EAE is mediated by CD4+ Th1 cells, which secrete pro-inflammatory mediators, and spontaneous recovery is mediated by regulatory T cells. Recently, it was established that classically activated macrophages (M1 phenotype) play an important role in the initiation of EAE, while alternatively activated macrophages (M2 phenotype) contribute to spontaneous recovery from rat EAE. This review will summarize the neuroimmunological aspects of active monophasic EAE, which manifests as neuroinflammation followed by neuroimmunomodulation and/or neuroprotection, with a focus on the role of alternatively activated macrophages.
Animals ; Central Nervous System ; Encephalomyelitis, Autoimmune, Experimental ; Macrophages ; Myelin Basic Protein ; Neuroimmunomodulation ; Paralysis ; Rats ; T-Lymphocytes, Regulatory ; Th1 Cells

The aim of the present study was to investigate the modulatory role of activated 5-HT(3) receptors in the central amygdala (CeA) on mitogen concanavalin A (ConA)-stimulated proliferative response of thymocytes in rats and the underlying neuroendocrine regulation circuits. 1-phenylbiguanide (PBG), a putative selective 5-HT(3) receptor agonist, was administered by intraperitoneal (i.p.), bilateral intracerebroventriclular (i.c.v.), and bilateral intracentral amygdala (i.c.a.) injection. In addition, thymocytes isolated from untreated rats were incubated with PBG (at a range of concentrations of 1x10(-8)-1x10(-5) mol/L) in vitro in the presence and absence of ConA, in order to investigate any direct effect of PBG on the proliferation in vitro. MTT method was applied to demonstrate the effect of PBG on the proliferative response of thymocytes. An immunohistochemical SABC assay was used to describe the expression profiles of c-Fos-positive cells in different brain regions including the CeA, hippocampus, cortex, hypothalamus and periaqueductal gray (PAG) at 1, 2, 4 and 8 h after bilateral single-administration of PBG by i.c.a. (1.0 microg/side). Results showed that PBG (1x10(-8)-1x10(-5) mol/L) had no significant influence on the proliferative responses of the isolated thymocytes in vitro, no matter ConA was present or not. The proliferation of thymocytes stimulated by ConA was not significantly changed when PBG was administered by i.p. (0.5 mg/kg per day, for consecutive 5 d), whereas it was remarkably enhanced after bilateral i.c.v. injection of PBG (10 microg/side per day, for consecutive 5 d). Similarly, when PBG was injected bilaterally by i.c.a. (1.0 microg/side per day, for 1 d or consecutive 3, 5 and 7 d), a significantly enhanced proliferation occurred on the 1st day and continued until reaching its peak on the 5th day before decreasing on the 7th day. All of the promoting effects of PBG on the ConA-stimulated proliferation of thymocytes were reversed by pretreatment with the 5-HT(3) receptor antagonist tropisetron (TRP) 5 min prior to the administration of PBG. Interestingly, compared to the treatment with normal saline or TRP + PBG, after a bilateral single-administration of PBG (1.0 microg/side) by i.c.a., the number of c-Fos-positive cells in different brain regions significantly increased at 1 h in the CeA, 1-2 h in the hippocampus, 1-2 h in the cortex, 4 h in the hypothalamus and 8 h in the PAG, respectively, with each maximum response at 1 h in the CeA, 2 h in the hippocampus and cortex, and 4 h in the hypothalamus. Subsequently, the number of cells expressing c-Fos gradually reduced to the minimum at 4 h in the CeA, and at 8 h in the hippocampus, cortex and hypothalamus. In conclusion, the 5-HT(3) receptors in the CeA of rats mediate the modulation of thymus function, at least partly, through the neuroendocrine circuit of the limbic system-cortex-hypothalamus-PAG.
Amygdala ; metabolism ; physiology ; Animals ; Male ; Neuroimmunomodulation ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT3 ; metabolism ; physiology ; Thymus Gland ; cytology ; physiology

It has been well known that catecholamines (CAs) in the body, including norepinephrine (NE), epinephrine (E) and dopamine (DA), are synthesized and secreted by neurons and endocrine cells and mainly modulate visceral activities such as cardiovascular, respiratory and digestive functions. The studies over the past nearly 30 years have shown that CAs can also regulate immune function. The immunomodulation of CAs is generally considered as a role mediating the regulation of nervous and endocrine systems. However, recent studies reveal that immune cells can also synthesize CAs, which is an update of traditional concept. A classical metabolic pathway of CAs shared by the nervous and endocrine systems is present in the immune cells, i.e., the immunocytes have the enzymes for synthesis of CAs [e.g. tyrosine hydroxylase (TH)] and the enzymes for degradation of CAs [e.g. monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)]. The endogenous CAs synthesized by immune cells can regulate many immune functions, including cellular proliferation, differentiation, apoptosis and cytokine production. These roles of the endogenous CAs may be mediated by an autocrine/paracrine pathway via relevant receptors on the immunocytes and intracellular cAMP. Intracellular oxidative mechanism may also be involved in immunoregulation of endogenous CAs in immune cells. In addition, some metabolic abnormalities of CAs in the immune cells probably induce some autoimmune diseases, such as multiple sclerosis (MS) and rheumatoid arthritis. These findings not only provide evidence for the new concept that the immune system is possible to become the third CA system other than the nervous and endocrine systems, but also extend our comprehension on functional significance of the endogenous CAs synthesized by immune cells.
Animals ; Autoimmune Diseases ; immunology ; Catecholamines ; physiology ; Humans ; Immune System ; physiology ; Lymphocytes ; immunology ; metabolism ; Monoamine Oxidase ; physiology ; Neuroimmunomodulation ; physiology ; Tyrosine 3-Monooxygenase ; physiology

AIMTo explore the effect of cerebellar fastigial nuclei (FN)on lymphocyte function and the pathway mediating the effect.

METHODSKainic acid (KA) was microinjected into bilateral FN of rats to destroy neuronal bodies in the FN. On the eighth day after the surgery, lymphocyte percentage in the peripheral blood and level of sheep red blood cell(SRBC)-specific IgM antibody in the serum were measured by using blood corpuscle counter and enzyme-linked immunosorbent assay (ELISA), respectively.A technology of electrolytic lesion was used to destroy the projections of cerebellar FN neurons to hypothalamus in decussation of superior cerebellar peduncle(xscp).

RESULTSOn the eighth day after the microinjection of KA into the bilateral FN of rats, the Nissl-stained neuronal bodies in the FN disappeared and glia could proliferated within the damaged FN. In the nuclei close to FN, the interposed nuclei and the dentate nuclei, Nissl-stained neurons still could be seen. On the control cerebellar sections, in which FN was infused with saline, we could see the normal Nissl-stained neurons in the FN and the other two nuclei.On day 8 following the effective FN lesions, both the lymphocyte percentage in the peripheral blood and the level of anti-SRBC IgM antibody in the serum were significantly increased in comparison with those of control rats infused with saline in the FN. On the eighth day after electrolytic lesion of the fibres in xscp, the FN-hypothalamic projections were damaged and there were no visible BDA-positive endings in hypothalamus. Meanwhile, both the lymphocyte percentage in the peripheral blood and the level of anti-SRBC IgM antibody in the serum were remarkably enhanced relative to those of control rats with sham lesion of xscp.

CONCLUSIONThe electrolytic lesion of the FN-hypothalamic projections in xscp causes an enhancement of lymphocyte function similar to that of KA lesions of neuronal soma in the FN. These findings suggest that the cerebellohypothalamic projections participate in mediating the modulation of lymphocyte function by the cerebellum.

Animals ; Cerebellar Nuclei ; immunology ; injuries ; Female ; Hypothalamus ; immunology ; physiology ; Kainic Acid ; Lymphocyte Count ; Lymphocytes ; cytology ; immunology ; Male ; Neural Pathways ; immunology ; physiology ; Neuroimmunomodulation ; physiology ; Rats ; Rats, Sprague-Dawley

Aging ; genetics ; physiology ; Diagnosis, Differential ; Humans ; Hypothalamo-Hypophyseal System ; physiology ; Kidney ; physiology ; Medicine, Chinese Traditional ; Neuroimmunomodulation ; physiology ; Pituitary-Adrenal System ; physiology ; Thymus Gland ; physiology ; Yang Deficiency ; physiopathology