Immunoregulation mediated by the sympathetic nervous system
Abstract
A postulated immunoregulatory role for the autonomous nervous system was explored utilizing several in vivo and in vitro approaches. Local surgical denervation of the spleen in rats and general chemical sympathectomy by 6-hydroxydopamine combined with adrenalectomy yielded a similar removal of restraint expressed as enhancement in the number of PFC in response to immunization. Noradrenaline and the synthetic α-agonist clonidine which are, respectively, natural and artificial effector molecules of the sympathetic nervous system each strongly suppressed the in vitro induced immune response of murine spleen cells to SRBC. Further, radiometric-enzymatic assay of noradrenaline in the splenic pulp revealed a decrease in the content of this neurotransmitter just preceding the exponential phase of the immune response to SRBC (Days 3 and 4) in this site. Taken together, these findings point to a dynamic immunoregulatory relationship between the immune and sympathetic nervous system.
References (43)
- B.H. Waksman et al.
Cell. Immunol
(1976) - D.H. Katz
- J.W. Hadden et al.
Cell. Immunol
(1970) - J.W. Hadden et al.
- C.W. Parker
- M. Da Prada et al.
Life Sci
(1976) - N.K. Jerne
Ann. Immunol. (Inst. Pasteur)
(1974) - T.A. Waldmann et al.
Science
J. Cell Physiol
J. Immunol
Eur. J. Immunol
J. Immunol
Nature (London)
J. Immunol
Cited by (399)
The inflammatory reflex reloaded
2022, Brain, Behavior, and ImmunityFeature and relationship between electroencephalogram power and salivary S-IgE concentration in healthy adults in different indoor temperatures
2022, Building and EnvironmentObtaining neural information about salivary secretory immunoglobulin E (S-IgE) is a starting point for investigating the mechanism of thermal environment regulation affecting human respiratory mucosal immunity. However, there is a scarcity of human-subjects research. To fill this void, we designed seven temperature conditions (15, 18, 21, 24, 27, 30, and 33 °C), collected electroencephalogram (EEG) and saliva from subjects, obtained thermal sensation and comfort votes, and detected S-IgE concentrations in saliva. Our results showed that the mean thermal sensation vote decreased by 2.31 units in the cold condition but increased by 2.25 units in the hot condition as compared to the thermal neutral condition (24 °C). Similarly, the absolute power of most channels in different frequency bands was the lowest at 24 °C within the thermally acceptable temperature range, including F8, F4, AF4, and T8 in α and β bands; at this temperature, the S-IgE concentration was the highest, increasing by 49.4 and 54.4%, respectively, compared to 21 and 27 °C. Furthermore, higher S-IgE concentration was associated with an increase in absolute power in the AF3 channel from the alpha band and the T8 channel from the theta band but a decrease in absolute power in the F7, T8, FC6, and F8 channels from the beta band (p < 0.05). Our findings suggest that EEG can be used to collect EEG signals associated to S-IgE concentration. Future research will concentrate on the effects of long-term temperature exposure on EEG signal and S-IgE concentration, as well as the link between them.
The autonomic inflammatory reflex
2022, Primer on the Autonomic Nervous System, Fourth EditionImmune challenges are detected by the CNS, which then activates a sympathetic nerve pathway whose function is to dampen down the systemic inflammatory response to the immune challenge, in negative feedback manner. The afferent pathways whereby the CNS is informed of the immune challenge may be humoral and/or neural, but are not fully defined. The efferent pathway of the inflammatory reflex is in the splanchnic sympathetic nerves. Its antiinflammatory actions are mediated by several abdominal viscera, not just the spleen. When activated by systemic immune challenge, the reflex suppresses proinflammatory cytokine responses while enhancing antiinflammatory cytokine release. This reflex action is powerful, and can strongly influence the outcome of systemic bacterial infection. It appears to be a basic biological phenomenon that transcends species. Its full implications remain to be worked out.
Reflex regulation of systemic inflammation by the autonomic nervous system
2022, Autonomic Neuroscience: Basic and ClinicalThis short review focusses on the inflammatory reflex, which acts in negative feedback manner to moderate the inflammatory consequences of systemic microbial challenge. The historical development of the inflammatory reflex concept is reviewed, along with evidence that the endogenous reflex response to systemic inflammation is mediated by the splanchnic sympathetic nerves rather than by the vagi. We describe the coordinated nature of this reflex anti-inflammatory action: suppression of pro-inflammatory cytokines coupled with enhanced levels of the anti-inflammatory cytokine, interleukin 10. The limited information on the afferent and central pathways of the reflex is noted. We describe that the efferent anti-inflammatory action of the reflex is distributed among the abdominal viscera: several organs, including the spleen, can be removed without disabling the reflex. Understanding of the effector mechanism is incomplete, but it probably involves a very local action of neurally released noradrenaline on beta2 adrenoceptors on the surface of tissue resident macrophages and other innate immune cells. Finally we speculate on the biological and clinical significance of the reflex, citing evidence of its power to influence the resolution of experimental bacteraemia.
The endogenous inflammatory reflex inhibits the inflammatory response to different immune challenges in mice
2021, Brain, Behavior, and ImmunityThe splanchnic anti-inflammatory pathway, the efferent arm of the endogenous inflammatory reflex, has been shown to suppress the acute inflammatory response of rats to systemic lipopolysaccharide (LPS). Here we show for the first time that this applies also to mice, and that the reflex may be engaged by a range of inflammatory stimuli. Experiments were performed on mice under deep anaesthesia. Half the animals were subjected to bilateral section of the splanchnic sympathetic nerves, to disconnect the splanchnic anti-inflammatory pathway, while the remainder underwent a sham operation. Mice were then challenged intravenously with one of three inflammatory stimuli: the toll-like receptor (TLR)-4 agonist, LPS (60 µg/kg), the TLR-3 agonist Polyinosinic:polycytidylic acid (Poly I:C, 1 mg/kg) or the TLR-2 and -6 agonist dipalmitoyl-S-glyceryl cysteine (Pam2cys, 34 µg/kg). Ninety minutes later, blood was sampled by cardiac puncture for serum cytokine analysis. The splanchnic anti-inflammatory reflex action was assessed by comparing cytokine levels between animals with cut versus those with intact splanchnic nerves. A consistent pattern emerged: Tumor necrosis factor (TNF) levels in response to all three challenges were raised by prior splanchnic nerve section, while levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were reduced. The raised TNF:IL-10 ratio after splanchnic nerve section indicates an enhanced inflammatory state when the reflex is disabled. These findings show for the first time that the inflammatory reflex drives a coordinated anti-inflammatory action also in mice, and demonstrate that its anti-inflammatory action is engaged, in similar fashion, by inflammatory stimuli mimicking a range of bacterial and viral infections.
Ionic liquid based ultrasound assisted dispersive liquid-liquid micro-extraction for simultaneous determination of 15 neurotransmitters in rat brain, plasma and cell samples
2018, Analytica Chimica ActaNeurotransmitters are signaling molecules which play a key role in the central nervous system allowing signal transmission in the neuronal synapses. The role of these compounds is very crucial in the biological systems. A rapid, sensitive, economical and derivatisation free method has been developed for the analysis of 15 neurotransmitters in a single run on liquid chromatography tandem mass spectrometry. These 15 neurotransmitters are categorized into 5 groups on the basis of their fragmentation pattern. The proposed method “ionic liquid based ultrasound assisted dispersive liquid-liquid microextraction” hyphenated with tandem mass spectrometry is the first report for the analysis of neurotransmitters in cell samples along with other two matrices (rat brain and plasma). All the parameters that influence the extraction efficiency are optimized with aid of response surface methodology and desirability profile. Under these optimized conditions the developed method has been validated. The limit of detection was in the range of (1) 0.021–0.912 μg L−1 for rat brain samples, (2) 0.028–0.978 μg L−1 for plasma samples and (3) 0.025–0.945 μg L−1 for cell samples with good linearity behavior for all analytes in the concentration range of 0.04–200 μg L−1 in all the three matrices. The coefficient of determination for all the neurotransmitters was found in the range of (1) (R2) ≥ 0.996 to 0.999 for rat brain samples and (2) (R2) ≥ 0.991 to 0.999 for plasma and cell samples. The intra-day and inter-day variations were found less than (1) 1.78% and 8.94% for rat brain samples, (2) 1.83% and 8.37% for plasma samples and (3) 1.64% and 8.04% for cell samples respectively. The method has mean recoveries varied between (1) 81–128% for brain samples, (2) 88–107% for plasma samples and (3) 91–104% for cell samples at different spiking levels. The optimized and validated method was found free from matrix interferences and successfully applied for quantitative determination of 15 neurotransmitters in the rat brain, plasma and cell samples.