Cytokines and feeding suppression: an integrative view from neurologic to molecular levels

Area of Science:

• Neuroscience
• Immunology
• Physiology

Background:

• Cytokines are released during infection, malignancy, and cytokine immunotherapy, often causing feeding suppression.
• Interleukin-1 beta (IL-1 beta), interferon (IFN), and IL-8 are examples of cytokines implicated in appetite regulation.

Purpose of the Study:

• To investigate the mechanisms by which cytokines, particularly IL-1 beta, suppress feeding behavior.
• To identify specific cytokine actions on hypothalamic neurons involved in appetite control.

Main Methods:

• Intracerebroventricular (ICV) microinfusion of cytokines (IL-1 beta, IFN, IL-8) and bacterial lipopolysaccharide in animal models.
• Administration of receptor antagonists and monoclonal antibodies to block cytokine effects.
• Electrophysiological recordings of neuronal activity in hypothalamic nuclei.

Main Results:

• IL-1 beta significantly reduced short- and long-term food intake by decreasing meal size and duration; higher doses also affected meal frequency.
• IFN and IL-8 primarily suppressed short-term feeding by reducing meal size and duration.
• Cytokine effects were blocked by receptor antagonists, confirming specificity.
• IL-1 beta and IFN directly modulated glucose-sensitive neurons in the ventromedial hypothalamus and lateral hypothalamus.
• Pathophysiological cytokine concentrations inhibited neuronal calcium channel currents.

Conclusions:

• Cytokines, especially IL-1 beta, play a significant role in regulating feeding behavior.
• Cytokines exert their appetite-suppressing effects through direct action on hypothalamic satiety and hunger centers.
• Understanding these neuro-immune interactions is vital for managing appetite loss in disease and during immunotherapy.