Chronic risperidone normalizes elevated pro-inflammatory cytokine and C-reactive protein production in omega-3 fatty acid deficient rats.
Prior clinical and preclinical studies suggest that omega-3 fatty acids negatively regulate pro-inflammatory signaling cascades, and that the atypical antipsychotic risperidone up-regulates omega-3 fatty acid biosynthesis. In the present study, we investigated the effects of chronic (40days) risperidone treatment (3mg/kg/day) on basal pro-inflammatory cytokine (interleukin-6, IL-6; tumor necrosis factor-alpha, TNFα) and C-reactive protein (CRP) production in control and n-3 fatty acid deficient rats. Relationships with erythrocyte polyunsaturated fatty acid composition were determined. Compared with untreated controls, untreated n-3-deficient rats exhibited significantly greater basal IL-6, TNFα, and CRP production. Following chronic risperidone treatment there were trends for greater IL-6, TNFα, and CRP production in controls, but these did not reach significance. In n-3-deficient rats, chronic risperidone normalized elevated IL-6, TNFα, and CRP levels. Erythrocyte arachidonic acid (20:4n-6) composition was positively correlated, and erythrocyte eicosapentenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) inversely correlated, with plasma IL-6, TNFα, and CRP levels in untreated control and n-3-deficient rats, and these associations were not observed among risperidone-treated rats. The adrenic acid (22:4n-6)/arachidonic acid ratio, an index of elongase-mediated arachidonic acid biosynthesis, was reduced by risperidone in controls and elevated in n-3-deficient rats. These preclinical data demonstrate that chronic risperidone treatment normalizes constitutively elevated pro-inflammatory cytokine and CRP production in n-3 fatty acid deficient rats but not in controls, and that the mechanism is dissociable from n-3 fatty acid biosynthesis.
Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45219, United States. robert.mcnamara@uc.edu
Robert K
RK
McNamara
Ronald
R
Jandacek
Therese
T
Rider
Patrick
P
Tso
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism*; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000145:classification / Q000378:metabolism*; D018752:Diet, Fat-Restricted / Q000379:methods; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D002097:C-Reactive Protein; D015118:Eicosapentaenoic Acid; D018967:Risperidone