Differential modulation of lipopolysaccharide- and zymosan-induced hypophagia by dexamethasone treatment.
The treatment of experimental animals with lipopolysaccharide (LPS) induces behavioral depression, in which the central and peripheral inductions of proinflammatory cytokines are proposed to play an important role. We have shown that the intraperitoneal injection of zymosan, composed of insoluble particles prepared from yeast cell walls, can induce behavioral depression assessed as hypophagia in mice, although the role of proinflammatory cytokines in this response has not yet been investigated. We have also shown that the subcutaneous injection of the corticoid, dexamethasone (Dex), a potent inhibitor of cytokine production, is effective in attenuating hypophagia in LPS-treated mice. The attenuated response was associated with the suppression of the gene induction of proinflammatory cytokines (i.e., IL-1beta, IL-6 and TNFalpha) in the brain and liver. In contrast, no significant induction of proinflammatory cytokine genes was observed in the brain or liver during zymosan-induced hypophagia; the subcutaneous injection of Dex did not attenuate zymosan-induced hypophagia but its intraperitoneal injection did. Thus, zymosan-induced hypophagia was less responsive to a subcutaneous injection of dexamethasone than LPS-induced hypophagia, which may be due to the limited role of systemic inflammation in this response. An important role of localized, rather than systemic, inflammation in zymosan-induced hypophagia was suggested, although the role of local proinflammatory cytokines remains to be clarified.
Saito
Masataka
M
Department of Clinical Application, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Watanabe
Shiro
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D015054:Zymosan; D004121:Dimethyl Sulfoxide