Straub, Rainer H. and Linde, Hans-Joerg and Maennel, Daniela N. and Schoelmerich, Juergen and Falk, Werner (2000) A bacteria-induced switch of sympathetic effector mechanisms augments local inhibition of TNF-alpha and IL-6 secretion in the spleen. FASEB JOURNAL, 14 (10). pp. 1380-1388. ISSN 0892-6638, 1530-6860
Full text not available from this repository. (Request a copy)Abstract
It is believed that an inflammation-induced activation of the CNS leads to an inhibition of overshooting immune responses to prevent extensive local cytokine secretion. However, immunosuppression by the sympathetic nervous system may be unfavorable when bacteria are present locally and when TNF-alpha is necessary to overcome infection. We now report in a superfusion model, using mouse spleen slices, that although local Pseudomonas aeruginosa increased splenic TNF-alpha and IL-6 secretion severalfold over basal levels, electrically released neurotransmitters attenuated cytokine secretion to similar basal level as under bacteria-free conditions. Bacteria reversed noradrenergic inhibitory effector mechanisms: Under bacteria-free conditions, TNF-alpha secretion was very low and IL-6 secretion was mainly inhibited by alpha(2)-adrenoreceptor ligation. In the presence of bacteria, TNF-alpha and IL-6 secretion were high and IL-6 secretion was mainly inhibited by beta-adrenoreceptor ligation. The alpha- to beta-adrenoswitch of IL-6 inhibition in the presence of bacteria was mediated by the prior adrenergic regulation of TNF-alpha. In vivo, chemical abrogation of sympathetic inhibition reduced accumulation of bacteria in the spleen, which depended at least in part on TNF-alpha. This suggests that activation of the sympathetic nervous system may be a forerunner for accumulation of bacteria in tissue and consecutively sepsis due to intensified inhibition of TNF-alpha secretion.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GRAM-NEGATIVE BACTERIA; NECROSIS-FACTOR-ALPHA; MURINE SPLEEN; INTERLEUKIN-6 SECRETION; NERVOUS-SYSTEM; TRANSLOCATION; EXPRESSION; SHOCK; LIPOPOLYSACCHARIDE; GLUCOCORTICOIDS; Pseudomonas aeruginosa; macrophage; tumor necrosis factor alpha; interleukin 6; norepinephrine; adrenoreceptor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Apr 2022 06:22 |
| Last Modified: | 05 Apr 2022 06:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42344 |
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