Cytokines and feeding suppression: an integrative view from neurologic to molecular levels.
Cytokines are released from activated cells during acute and chronic pathologic processes including infection and malignancy. These processes and immunotherapy with cytokines are frequently accompanied by feeding suppression. The intracerebroventricular (ICV) microinfusion of low doses of interleukin 1 beta (IL-1 beta) decreases short- and long-term food intake by reducing meal size and meal duration; high amounts also decrease meal frequency and prolong intermeal intervals. The ICV microinfusion of interferon (IFN) suppresses only short-term feeding by reducing meal size and meal duration; IL-8 suppresses short-term feeding by reducing meal size. Bacterial lipopolysaccharide also reduces meal size. IL-1 beta is significantly more potent than IFN, IL-8, and other cytokines. Evidence also shows that only a subset of cytokines released during pathologic processes participate in the regulation of feeding. These behavioral effects of cytokines are blocked by the appropriate receptor antagonists and monoclonal antibodies. Cytokines affect the hypothalamus and this may result in feeding suppression. IL-1 beta and IFN act directly and specifically on the glucose-sensitive neurons in the ventromedial hypothalamic nucleus (a "satiety" site) and the lateral hypothalamic area (a "hunger" site). Pathophysiologic concentrations of IL-1 beta and IL-2 in the cerebrospinal fluid inhibit the calcium channel current in neurons. It is essential to characterize the mechanisms by which cytokines induce feeding suppression to understand appetite suppression during disease and immunotherapy.
Plata-Salamán
C R
CR
Medical Sciences Faculty, School of Life and Health Sciences, University of Delaware, Newark 19716, USA.
D000818:Animals; D001067:Appetite Depressants; D001069:Appetite Regulation; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D009747:Nutritional Physiological Phenomena
D001067:Appetite Depressants; D016207:Cytokines; D007378:Interleukins