Defective inflammatory response in interleukin 6-deficient mice.
Open accessAbstract
Systemic and localized inflammation elicit a number of host responses which include fever, cachexia, hypoglycemia, and major changes in the concentration of liver plasma proteins. Interleukin 6 (IL-6) is considered an important mediator of the inflammatory response, together with IL-1 and tumor necrosis factor alpha (TNF-alpha). The purpose of this study was to unequivocally determine the role of IL-6 in these phenomena making use of IL-6-deficient mice that we have recently generated by gene targeting. We report here that in the absence of IL-6, mice are unable to mount a normal inflammatory response to localized tissue damage generated by turpentine injection. The induction of acute phase proteins is dramatically reduced, mice do not lose body weight and only suffer from mild anorexia and hypoglycemia. In contrast, when systemic inflammation is elicited through the injection of bacterial lipopolysaccharide (LPS), these parameters are altered to the same extent both in wild-type and IL-6-deficient mice, demonstrating that under these conditions IL-6 function is dispensable. Moreover, we show that LPS-treated IL-6-deficient mice produce three times more TNF-alpha than wild-type controls, suggesting that increased TNF-alpha production might be one of the compensatory mechanisms through which a normal response to LPS is achieved in the absence of IL-6. We also show that corticosterone is normally induced in IL-6-deficient mice, demonstrating that IL-6 is not required for the activation of the hypothalamic-pituitary-adrenal axis. Our results reinforce the idea that different patterns of cytokines are involved in systemic and localized tissue damage, and identify IL-6 as an essential mediator of the inflammatory response to localized inflammation.
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IL-6 KO mice do not have a normal rise in plasma corticosterone after LPS injection, in contrast to Fattori et al. (39).
“In contrast to Fattori et al. (39), our data show that IL-6 KO mice do not have a normal rise in plasma corticosterone after LPS injection.”
From Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation (2000) · cites this paper as [39]
The relatively slow IL-6 response explains why corticosterone responses have previously been shown to be normal in IL-6-/- and IL-1-/- mice after TPS when evaluated at 1.5-2 h.
“The relatively slow IL-6 response explains why corticosterone responses have previously been shown to be normal in IL-6 Ϫ/Ϫ and IL-1 Ϫ/Ϫ mice after the injection of TPS, as corticosterone responses were evaluated at 1.5-2 h thereafter (20 -22) and is consistent with our finding that stressinduced corticosterone responses are similar in IL-6 ϩ/ϩ and IL-6 Ϫ/Ϫ mice.”
From Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice (2003) · cites this paper as [20]
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“IL-6-deficient mice cannot mount a normal inflammatory response to localized tissue damage induced by turpentine treatment and the expression of induced acute phase proteins goes an apparent decline (50).”
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“To provide a basis for our ex vivo experiments and to enable model predictions of physiological relevance, we determined physiological IL-6 concentrations in mice following partial hepatectomy (PHx; Mitchell and Willenbring, 2008) and lipopolysaccharide (LPS) injection (Fattori et al., 1994; Copeland et al., 2005), wh…”
Method
- Authors
- Fattori, E., Cappelletti, M., Costa, P., Sellitto, C., Cantoni, L., Carelli, M., Faggioni, R., Fantuzzi, G., Ghezzi, P., & Poli, V
- Affiliations
- Istituto di Ricerche di Biologia Molecolare IRBM P. Angeletti, Pomezia, Roma.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1994-10-01
- Volume
- 180
- Issue
- 4
- Pages
- 1243-1250
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2191674
- OpenAlex
- W2057018521
- Cited by
- 525
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 8 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 5 · 2017: 15 · 2016: 7 · 2015: 7 · 2014: 13 · 2013: 11 · 2012: 17
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- interleukin-6, IL-6-deficient mice, inflammation, local inflammation, systemic inflammation, acute phase proteins, hypoglycemia, cachexia, lipopolysaccharide, TNF-α, corticosterone, hypothalamic-pituitary-adrenal axis
- MeSH terms
- Acute-Phase Reaction, Serum Amyloid A Protein, Animals, Anorexia, Corticosterone, Hypoglycemia, Inflammation, Interleukin-1, Lipopolysaccharides, Liver, Tumor Necrosis Factor-alpha, Turpentine, Interleukin-6, Mice
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