title: Ciglitazone increases basal cytokine expression in the central nervous system of adult rats.
abstract: Ciglitazone, rosiglitazone, and pioglitazone belong to a relatively new class of antidiabetic agents referred to as thiazolidinediones (TZDs). Later, TZDs were found to be peroxisome proliferator-activated receptor (PPAR)-gamma agonists and to elicit anti-inflammatory effects in both in vitro and in vivo models in response to stimuli such as lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA). In the present study, we sought to investigate the effects of oral administration of ciglitazone on basal inflammatory cytokine expression in healthy adult rats. The analysis of cytokine expression in the spleen revealed a reduction in IL-4 production after ciglitazone treatment. In contrast, in the brain, ciglitazone administration increased IL-1beta synthesis at the protein and mRNA level, while TNF-alpha protein expression was also increased. To ensure that the latter findings were not an indirect effect originating from the periphery, we delivered ciglitazone intracerebrally for a 7-day period using an osmotic pump, which confirmed the increase in IL-1beta and TNF-alpha expression. Our results show that despite anti-inflammatory effects described for ciglitazone in "primed" models, ciglitazone can positively modulate basal inflammatory mediators within the central nervous system (CNS) of healthy adult rodents.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, 6 Queen's Park Crescent West, Toronto, Ontario, Canada M5S3H2.
authors.forename: David S
authors.initials: DS
authors.lastname: Gélinas
authors.forename: Mark H L
authors.initials: MH
authors.lastname: Lambermon
authors.forename: JoAnne
authors.initials: J
authors.lastname: McLaurin
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007260:Infusion Pumps; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D007375:Interleukin-1; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C039671:ciglitazone