Interferon-Gamma Release in Sympathetically Denervated Rat Submaxillary Lymph Nodes

Abstract

Objective: To examine the regulation of interferon (IFN)-γ release by cells derived from submaxillary lymph nodes of rats subjected to an acute or chronic superior cervical ganglionectomy (SCGx). Methods: A unilateral SCGx and a contralateral sham operation were performed. Twenty hours or 7 days later cells from submaxillary lymph nodes were incubated for 24 h without any additional treatment (experiment 1), after adding lipopolysaccharide or concanavalin A (experiment 2) or after adding norepinephrine (NE, 10^–8M; experiment 3). IFN-γ concentration in the culture media was measured by ELISA. Results: Compared to controls, cells obtained from lymph nodes at a time of degeneration of sympathetic nerve terminals released more IFN-γ, whereas those derived from chronically SCGx lymph nodes released less IFN-γ. Stimulation of IFN-γ release by mitogens was detectable in the innervated or acutely denervated lymph nodes, but not in chronically denervated lymph nodes. When the effect of 10^–8M NE on IFN-γ release was tested, the neurotransmitter augmented cytokine release in cells prepared from chronically denervated lymph nodes only. Conclusion: The microenvironment provided by local sympathetic nerves is essential to enable an appropriate IFN-γ release by submaxillary lymph node cells to occur.

Neuronally released sympathetic neurotransmitters stimulate splenic interferon‐γ secretion from T cells in early type II collagen–induced arthritis

“…It was shown that norepinephrine, via ␤ 2 -adrenergic receptors, stimulates IFN␥ secretion from naive precursor T cells while they differentiate into IFN␥-producing cells, but that a ␤ 2 -adrenergic agonist inhibited already IFN␥-producing, newly generated ef- fector Th1 cells (28). These dual effects of norepinephrine on T cells might well explain some of the contrasting results reported in the literature, because several authors demonstrated inhibitory effects of norepinephrine on IFN␥ secretion (28)(29)(30)(31)(32) and others showed stimulatory effects (19,(33)(34)(35)(36).…”

“…Only in chronically and surgically denervated submaxillary lymph nodes was norepinephrine able to stimulate IFNγ secretion from lymph node cells, but the effect was opposite in acutely denervated submaxillary lymph nodes (34). These effects cannot be explained by a change in leukocyte subsets in the submaxillary lymph node, because chronic denervation over 7 days had no influence (34). Thus, the findings might be explained by receptor sensitization in the absence of the endogenous agonist.…”

“…The question remains as to why there are still any ␤-adrenergic effects when the density of splenic sympathetic nerve fibers starts to decrease and the norepinephrine concentration gets lower. Importantly, it was demonstrated that the influence of norepinephrine on IFN␥ secretion depended on the degree of sympathetic innervation of the target lymphoid organ (34). Only in chronically and surgically denervated submaxillary lymph nodes was norepinephrine able to stimulate IFN␥ secretion from lymph node cells, but the effect was opposite in acutely denervated submaxillary lymph nodes (34).…”

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“…IFN-γ concentration in media culture was measured after centrifugation to remove adherent cells. An ELISA commercial kit from Endogen (Woburn, MA, USA), previously validated in our laboratory, was employed [16]. The assay was performed as follows: 100 μl of standards or unknown samples were added to each antibody-coated well, and the plates were incubated overnight at room temperature.…”

Autonomic Nervous System Influences on HIV Pathogenesis

“…Sympathetic fibers reach paracortical, medullary, and interfollicular cor-tical regions but avoid nodular regions and germinal centers (Felten and Olschowka, 1987;Fink and Weihe, 1988). Several lines of evidence suggest that autonomic innervation of lymphoid tissue may affect immune function (Madden et al, 1995a(Madden et al, , 1995bDowning and Miyan, 2000;Castrillon et al, 2000), but little is known about its impact on lymphotropic viruses. We mapped the distribution of catecholaminergic neurons in lymph nodes from SIV-infected macaques using sucrose phosphate glyoxylic acid (SPG) chemofluorescence and carried out spatial statistical analyses to determine whether SIV replication was increased in the near vicinity.Active SIV replication was mapped by in situ hybridization to gag, pol, and nef mRNA.…”