An approach to study molecular mechanisms involved in cytokine-induced anorexia.
Cytokines are released during pathophysiological processes. Cytokines (e.g., interleukin-1 beta or IL-1 beta) induce neurological manifestations including anorexia. Here, we show an integrative approach to investigate the cellular and molecular basis of cytokine-induced anorexia. In this approach: (1) the chronic intracerebroventricular (icv) microinfusion (via osmotic minipumps) of cytokines, at doses that will yield estimated pathophysiological concentrations reported in the cerebrospinal fluid, is used. (2) General and computerized behavioral monitoring characterizes the microstructure of behavioral modifications induced by a cytokine, and the time course for cytokine action. (3) Brain regions and subregions (nuclei/areas) from animals exhibiting significant anorexia in response to cytokine(s) are dissected, and RNA and protein are isolated. (4) The profile of cytokine subsystems (ligands, receptors, endogenous inhibitors; for example, IL-1 alpha and beta, IL-1 receptor types I and II, and IL-1 receptor antagonist) is characterized in the same brain samples with polymerase chain reaction, sensitive RNase protection assays and immunoblots. (5) The relationship between changes in cytokine subsystems at the molecular level and cytokine-induced anorexia within an animal is determined, and the general profile is analyzed with statistical methods. This approach is also pertinent to study neurotransmitter and neuropeptide profiles, and cytokine-cytokine, cytokine-neuropeptide and cytokine-neurotransmitter interactions in vivo. The results show that this integrative and novel strategy can be used to study the molecular basis of anorexia and other neurological manifestations (e.g., fever, sleep changes) induced by cytokines.
Ilyin
S E
SE
School of Life and Health Sciences, University of Delaware, Newark 19716-2590, USA.
Plata-Salamán
C R
CR
D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry; D004327:Drinking Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D007276:Injections, Intraventricular / Q000295:instrumentation*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000235:genetics / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000187:drug effects* / Q000502:physiology; D012795:Sialoglycoproteins / Q000494:pharmacology
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins