An imbalance in the production of IL-1beta and IL-6 by monocytes of bipolar patients: restoration by lithium treatment.
OBJECTIVE
To study the ex vivo interleukin (IL)-1beta and IL-6 production of monocytes in bipolar disorder (BD) patients in the absence/presence of lithium.


METHODS
Monocytes of outpatients with DSM-IV BD (n=80, of whom 64 were lithium-treated) and of healthy control subjects (n=59) were cultured in vitro and exposed (24 h) or not exposed to lipopolysaccharide (LPS) and/or graded concentrations of lithium chloride (LiCl). IL-1beta and IL-6 production was assessed by enzyme-linked immunosorbent assay (ELISA) (supernatants).


RESULTS
Monocytes stimulated by LPS from non-lithium-treated bipolar patients were characterized by an abnormal IL-1beta/IL-6 production ratio, i.e., low IL-1beta and high IL-6 production. Lithium treatment increased IL-1beta and decreased IL-6 production and thus restored the aberrant ratio. In vitro exposure of monocytes to LiCl did not have the same effects as lithium treatment: the procedure decreased IL-1beta production and had minimal effects on IL-6 production.


CONCLUSIONS
Blood monocytes have an altered proinflammatory status in BD. Lithium treatment restores this altered status. Short-term in vitro exposure of monocytes to lithium has other effects than lithium treatment.
Knijff
Esther M
EM
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands. e.knijff@erasmusmc.nl
Breunis
M Nadine
MN
Kupka
Ralph W
RW
de Wit
Harm J
HJ
Ruwhof
Cindy
C
Akkerhuis
Grard W
GW
Nolen
Willem A
WA
Drexhage
Hemmo A
HA
D000328:Adult; D000553:Ambulatory Care; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D002478:Cells, Cultured; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000627:therapeutic use
D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018020:Lithium Compounds; D011619:Psychotropic Drugs; D018021:Lithium Chloride