MicroRNA-155 potentiates the inflammatory response in hypothermia by suppressing IL-10 production

Area of Science:

• Immunology
• Molecular Biology
• Physiology

Background:

• Therapeutic hypothermia improves neurological outcomes post-cardiac arrest but increases sepsis risk.
• Unintentional hypothermia in surgery correlates with infectious complications.
• Molecular mechanisms of hypothermia-induced innate immune dysregulation remain unclear.

Purpose of the Study:

• Investigate how hypothermia affects innate immune responses.
• Elucidate the role of microRNA-155 (miR-155) in hypothermia-induced immune dysregulation.
• Determine the impact of miR-155 on inflammatory cytokine production and patient outcomes.

Main Methods:

• Exposed human monocytes to cold (32°C) and stimulated with lipopolysaccharide (LPS).
• Measured cytokine production (TNF, IL-6, IL-10) and expression of miR-155, Ship1, and Socs1.
• Utilized miR-155 antagomirs and mimics to assess functional effects.
• Employed a murine model of LPS-induced peritonitis under cold exposure.
• Assessed survival rates and immune markers in miR-155-deficient mice.

Main Results:

• Cold exposure potentiated LPS-induced TNF and IL-6, while blunting IL-10 production in monocytes.
• Hypothermia increased miR-155 expression, suppressing Ship1 and Socs1.
• miR-155 inhibition reversed cold-induced cytokine alterations; miR-155 mimics replicated them.
• In mice, cold exposure increased miR-155, suppressed Ship1/Socs1, reduced survival, and altered cytokine profiles.
• miR-155 deficiency improved survival and normalized immune responses under hypothermia.

Conclusions:

• Hypothermia dysregulates innate immunity through increased miR-155.
• miR-155 negatively regulates Ship1 and Socs1, impacting Toll-like receptor signaling.
• miR-155 plays a causal role in hypothermia-induced immune dysfunction and reduced survival.
• Targeting miR-155 may offer therapeutic potential for managing immune complications during hypothermia.