{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:25:20Z","timestamp":1786620320192,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T00:00:00Z","timestamp":1663459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>The efferent branches of the splanchnic sympathetic nerves that enhance interleukin\u201010 (IL\u201010) and suppress tumour necrosis factor\u2010\u03b1 (TNF) levels in the reflex response to systemic immune challenge were investigated in anaesthetized, ventilated rats. Plasma levels of TNF and IL\u201010 were measured 90\u00a0min after intravenous lipopolysaccharide (LPS, 60\u00a0\u00b5g\/kg). Splanchnic nerve section, ganglionic blockade with pentolinium tartrate or \u03b2<jats:sub>2<\/jats:sub> adrenoreceptor antagonism with ICI 118551 all blocked IL\u201010 responses. Restoring plasma adrenaline after splanchnic denervation rescued IL\u201010 responses. TNF responses were disinhibited by splanchnic denervation or pentolinium treatment, but not by ICI 118551. Splanchnic nerve branches were cut individually or in combination in vagotomized rats, ruling out any vagal influence on results. Distal splanchnic denervation, sparing the adrenal nerves, disinhibited TNF but did not reduce IL\u201010 responses. Selective adrenal denervation depressed IL\u201010 but did not disinhibit TNF responses. Selective denervation of either spleen or liver did not affect IL\u201010 or TNF responses, but combined splenic and adrenal denervation did so. Finally, combined section of the cervical and lumbar sympathetic nerves did not affect cytokine responses to LPS. Together, these results show that the endogenous anti\u2010inflammatory reflex is mediated by sympathetic efferent fibres that run in the splanchnic, but not other sympathetic nerves, nor the vagus. Within the splanchnic nerves, divergent pathways control these two cytokine responses: neurally driven adrenaline, acting via \u03b2<jats:sub>2<\/jats:sub> adrenoreceptors, regulates IL\u201010, while TNF is restrained by sympathetic nerves to abdominal organs including the spleen, where non\u2010\u03b2<jats:sub>2<\/jats:sub> adrenoreceptor mechanisms are dominant.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15242-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>An endogenous neural reflex, mediated by the splanchnic, but not other sympathetic nerves, moderates the cytokine response to systemic inflammatory challenge. This reflex suppresses the pro\u2010inflammatory cytokine tumour necrosis factor\u2010\u03b1 (TNF), while enhancing levels of the anti\u2010inflammatory cytokine interleukin\u201010 (IL\u201010).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The reflex enhancement of IL\u201010 depends on the splanchnic nerve supply to the adrenal gland and on \u03b2<jats:sub>2<\/jats:sub> adrenoreceptors, consistent with mediation by circulating adrenaline. After splanchnic nerve section it can be rescued by restoring circulating adrenaline.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The reflex suppression of TNF depends on splanchnic nerve branches that innervate abdominal tissues including, but not restricted to, spleen: it is not blocked by adrenal denervation or \u03b2<jats:sub>2<\/jats:sub> adrenoreceptor antagonism.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Distinct sympathetic efferent pathways are thus responsible for pro\u2010 and anti\u2010inflammatory cytokine components of the reflex regulating inflammation.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283217","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T04:34:10Z","timestamp":1662179650000},"page":"4521-4536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Divergent splanchnic sympathetic efferent nerve pathways regulate interleukin\u201010 and tumour necrosis factor\u2010\u03b1 responses to endotoxaemia"],"prefix":"10.1113","volume":"600","author":[{"given":"Michael J.","family":"McKinley","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Victoria Australia"},{"name":"Department of Anatomy and Physiology University of Melbourne  Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-9598","authenticated-orcid":false,"given":"Davide","family":"Martelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences Physiology Division University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Trevizan\u2010Ba\u00fa","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Victoria Australia"},{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne  Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7979-5656","authenticated-orcid":false,"given":"Robin M.","family":"McAllen","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,18]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.09.004"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120571"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706048"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00754.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00424-1"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2014.01.006"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(79)90129-1"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003152"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.5771"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2019.02.002"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705972"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-7443(07)00210-4"},{"key":"e_1_2_5_15_1","first-page":"595","article-title":"The sympathetic nerve\u2013an integrative interface between two supersystems: The brain and the immune system","volume":"52","author":"Elenkov I. 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