Skeletal Muscle INTERLEUKIN-6 Contributes to the Innate Immune Response in Septic MICE

Orlando Laitano, Gerard P Robinson, Christian K Garcia, Alex J Mattingly, Laila H Sheikh, Kevin O Murray, John D Iwaniec, Jamal Alzahrani, Deborah Morse, Juan Hidalgo Pareja, Thomas L Clanton

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

ABSTRACT: Interleukin-6 (IL-6) is a major cytokine released by skeletal muscle. Although IL-6 plays complex but well-known roles in host defense, the specific contribution of skeletal muscle IL-6 to innate immunity remains unknown. We tested its functional relevance by exposing inducible skeletal muscle IL-6 knockdown (skmIL-6KD) mice to a cecal slurry model of polymicrobial peritonitis and compared responses to strain-matched controls and skeletal muscle Cre-matched controls at 3, 6, and 12 h postinfection. In both sexes, skmIL-6KD mice at 6 h of infection exhibited marked changes to leukocyte trafficking in the peritoneum, characterized by ∼1.75-fold elevation in %neutrophils, a ∼3-fold reduction in %lymphocytes and a ∼2 to 3-fold reduction in %basophils. A similar pattern was seen at 12 h. No changes were observed in plasma leukocyte counts. Circulating cytokines in female skmIL-6KD mice at 6 h consistently showed modest reductions in IL-6, but marked reductions in a broad range of both pro- and anti-inflammatory cytokines, e.g., TNFα and IL-10. In both sexes at 12 h, a generalized suppression of plasma cytokines was also seen after the effects of Cre-induction with raloxifene were addressed. There were no significant effects of skmIL-6KD on mortality in either sex. Collectively, our results are consistent with skmIL-6 playing an important and previously unrecognized role in immune cell trafficking and cytokine regulation during septic shock.

Original languageAmerican English
Pages (from-to)676-685
Number of pages10
JournalShock (Augusta, Ga.)
Volume55
Issue number5
DOIs
Publication statusPublished - 1 May 2021

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