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Related Concept Videos

Inflammatory Response01:28

Inflammatory Response

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An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Related Experiment Video

Updated: Jan 8, 2026

Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
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Diurnally-Regulated Corticosterone and Melatonin Inversely Control Endotoxin-Induced Acute Immune Responses.

Montaser Haddad1, Sebastien Trzebanski1, Ramon Bossardi Ramos2

  • 1Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.

European Journal of Immunology
|December 18, 2025
PubMed
Summary

Mice challenged with lipopolysaccharide (LPS) in the afternoon have higher mortality due to inflammation than those challenged at midnight. Circadian hormones like corticosterone and melatonin regulate this diurnal variation in sepsis survival.

Keywords:
corticosteroneinflammationmelatoninneutrophils

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Area of Science:

  • Immunology
  • Chronobiology
  • Endocrinology

Background:

  • Diurnal variation in survival exists for endotoxin challenges, but mechanisms are unclear.
  • Host inflammatory responses to infection are influenced by circadian rhythms.

Purpose of the Study:

  • Investigate the mechanisms behind diurnal variation in sepsis survival.
  • Determine the role of circadian-regulated hormones in modulating inflammatory responses to lipopolysaccharide (LPS).

Main Methods:

  • Administered LPS to mice at different times of day (afternoon vs. midnight).
  • Measured inflammatory markers, neutrophil activation, and survival rates.
  • Assessed the impact of corticosterone and melatonin levels on immune responses.

Main Results:

  • Afternoon LPS challenges resulted in increased neutrophil activation, severe inflammation, and higher mortality compared to midnight challenges.
  • Corticosterone peaks in the afternoon exacerbated LPS-induced hyperinflammation.
  • Melatonin levels at midnight protected mice by reducing inflammatory responses.

Conclusions:

  • Circadian rhythms, specifically hormone cycles (corticosterone and melatonin), significantly impact sepsis outcomes.
  • Hormonal profiles in septic patients (high cortisol, low melatonin) resemble those in susceptible mice, suggesting a prognostic marker.
  • A regulatory network linking light/dark cycles and circadian hormones to inflammatory intensity in infection is identified.