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Interleukin-6 primarily produced by non-hematopoietic cells mediates the lipopolysaccharide-induced febrile response
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
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2013 (engelsk)Inngår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 33, s. 123-130Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Interleukin-6 (IL-6) is critical for the lipopolysaccharide (LPS)-induced febrile response. However, the exact source(s) of IL-6 involved in regulating the LPS-elicited fever is still to be identified. One known source of IL-6 is hematopoietic cells, such as monocytes. To clarify the contribution of hematopoietically derived IL-6 to fever, we created chimeric mice expressing IL-6 selectively either in cells of hematopoietic or, conversely, in cells of non-hematopoietic origin. This was performed by extinguishing hematopoietic cells in wild-type (WT) or IL-6 knockout (IL-6 KO) mice by whole-body irradiation and transplanting them with new stem cells. Mice on a WT background but lacking IL-6 in hematopoietic cells displayed normal fever to LPS and were found to have similar levels of IL-6 protein in the cerebrospinal fluid (CSF) and in plasma and of IL-6 mRNA in the brain as WT mice. In contrast, mice on an IL-6 KO background, but with intact IL-6 production in cells of hematopoietic origin, only showed a minor elevation of the body temperature after peripheral LPS injection. While they displayed significantly elevated levels of IL-6 both in plasma and CSF compared with control mice, the increase was modest compared with that seen in LPS injected mice on a WT background, the latter being approximately 20 times larger in magnitude. These results suggest that IL-6 of non-hematopoietic origin is the main source of IL-6 in LPS-induced fever, and that IL-6 produced by hematopoietic cells only plays a minor role.

sted, utgiver, år, opplag, sider
Elsevier , 2013. Vol. 33, s. 123-130
Emneord [en]
Interleukin-6, Hematopoietic cells, Bone marrow transplantation, Fever
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-99401DOI: 10.1016/j.bbi.2013.06.006ISI: 000324788300016OAI: oai:DiVA.org:liu-99401DiVA, id: diva2:656921
Merknad

Funding Agencies|Swedish Research Council|33X-0787968X-2053564X-21463|Swedish Cancer Foundation|4095|Swedish Brain Foundation||Tore Nilsson Foundation||Ake Wiberg Foundation||Langmanska Kulturfonden||Lars Hierta Memorial Foundation||Magn. Bergvall Foundation||County Council of Ostergotland||Harald and Greta Jeansson Foundation||Royal Swedish Academy of Sciences||Foundation of the National Board of Health and Welfare||

Tilgjengelig fra: 2013-10-17 Laget: 2013-10-17 Sist oppdatert: 2017-12-06

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