Interleukin-6 blockade, a potential adjunct therapy for post-burn hypermetabolism.
anti-IL-6 mAb
burn
effectiveness
hypermetabolism
interleukin-6
safety
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
29
03
2021
received:
04
03
2021
accepted:
31
03
2021
entrez:
19
4
2021
pubmed:
20
4
2021
medline:
20
7
2021
Statut:
ppublish
Résumé
Severe burns remain a leading cause of death and disability worldwide. Despite advances in patient care, the excessive and uncontrolled hypermetabolic stress response induced by this trauma inevitably affects every organ system causing substantial morbidity and mortality. Recent evidence suggests interleukin-6 (IL-6) is a major culprit underlying post-burn hypermetabolism. Indeed, genetic deletion of IL-6 alleviates various complications associated with poor clinical outcomes including the adverse remodeling of adipose tissue, cachexia and hepatic steatosis. Thus, pharmacological blockade of IL-6 may be a more favorable treatment option to fully restore metabolic function after injury. To test this, we investigated the safety and effectiveness of blocking IL-6 for post-burn hypermetabolism using a validated anti-IL-6 monoclonal antibody (mAb) in our experimental murine model. Here, we show daily anti-IL-6 mAb administration protects against burn-induced weight loss (P < .0001) without any adverse effect on mortality. At the organ level, post-burn treatment with the IL-6 blocker suppressed the thermogenic activation of adipose tissue (P < .01) and its associated wasting (P < .05). The reduction of browning-induced lipolysis (P < .0001) indirectly decreased hepatic lipotoxicity (P < .01) which improved liver dysfunction (P < .05). Importantly, the beneficial effects of this anti-IL-6 agent extended to the skin, reflected by the decrease in excessive collagen deposition (P < .001) and genes involved in pathologic fibrosis and scarring (P < .05). Together, our results indicate that post-burn IL-6 blockade leads to significant improvements in systemic hypermetabolism by inhibiting pathological alterations in key immunometabolic organs. These findings support the therapeutic potential of anti-IL-6 interventions to improve care, quality of life, and survival in burned patients.
Identifiants
pubmed: 33871073
doi: 10.1096/fj.202100388R
pmc: PMC8982752
mid: NIHMS1789588
doi:
Substances chimiques
Antibodies, Monoclonal
0
Interleukin-6
0
interleukin-6, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21596Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM087285
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM133961
Pays : United States
Organisme : NIH HHS
ID : R01GM087285
Pays : United States
Organisme : CIHR
ID : 123336
Pays : Canada
Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
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