title: The effects of lithium on ex vivo cytokine production.
abstract: BACKGROUND
  Studies suggest that lithium may have profound immunomodulatory effects in animal models as well as in humans.
  
  
  METHODS
  In this study, whole blood cultures from normal control subjects were established for 5 days and the effects of lithium on cytokine production were investigated. Because many of lithium's actions have been postulated to be modulated through phosphoinositide (PI), protein kinase C (PKC) and cyclic adenosine monophosphate (c-AMP) signaling pathways, the effects of myo-inositol and prostaglandin E(2), alone or in combination with lithium, were also investigated.
  
  
  RESULTS
  We found that lithium caused an increase in interleukin-4 and interleukin-10 levels, traditionally classified as T-helper lymphocyte type-2 cytokines, and a decrease in interleukin-2 and interferon-gamma levels, traditionally classified as T-helper lymphocyte type-1 (TH-1) cytokines. This shift cannot be fully explained by lithium's actions on the PI, PKC, or c-AMP messenger systems.
  
  
  CONCLUSIONS
  Monocytes exposed to lithium in the presence of a mitogen for 5 days produced a shift toward the production of TH-2 cytokines and away from the production of TH-1 cytokines. The study suggests that lithium may have complex time-dependent effects on immune function.
authors.affiliation: Psychopharmacology Research Program, Department of Psychiatry, University of California, San Diego, California 92037, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Rapaport
authors.forename: H K
authors.initials: HK
authors.lastname: Manji
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D016207:Cytokines; D008094:Lithium; D000242:Cyclic AMP; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase