In vivo immunomodulatory effects of clozapine in schizophrenia.
Recently, there have been some reports that schizophrenia is accompanied by an immune-inflammatory response, characterized by increased secretion of interleukin-6 (IL-6), soluble IL-2 receptor (sIL-2) and lower plasma levels of CC16 (Clara cell protein), an endogenous anti-cytokine. It was shown that clozapine, an atypical antipsychotic drug, may increase the plasma levels of sIL-2R and pro-inflammatory cytokines. This study was carried out in order to examine serum IL-6, IL-6R, CC16, IL-1R antagonist (IL-1RA), transferrin receptor (TfR) and sCD8 antigen, both before and after treatment with clozapine in schizophrenic subjects versus normal controls. Schizophrenic patients showed significantly higher plasma IL-6R and IL-1RA and lower plasma CC16 than normal controls. Treatment with clozapine significantly increased plasma sCD8, IL-6, CC16 and IL-1RA concentrations. The clozapine-induced increments in plasma IL-6 and CC16 appeared during the first 2 weeks of treatment, whereas the increases in plasma sCD8 and IL-1RA appeared after 5 weeks. Clozapine appears to have complex in vivo immunomodulatory effects.
Maes
M
M
Clinical Research Center for Mental Health, Antwerp, Belgium.
Bosmans
E
E
Kenis
G
G
De Jong
R
R
Smith
R S
RS
Meltzer
H Y
HY
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016827:CD8 Antigens / Q000097:blood / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000187:drug effects; D015213:Neuroimmunomodulation; D017472:Receptors, Interleukin-1 / Q000097:blood / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects; D019947:Receptors, Interleukin-6 / Q000097:blood / Q000187:drug effects; D011990:Receptors, Transferrin / Q000097:blood / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D016827:CD8 Antigens; D015850:Interleukin-6; D008565:Membrane Proteins; D017472:Receptors, Interleukin-1; D015375:Receptors, Interleukin-2; D019947:Receptors, Interleukin-6; D011990:Receptors, Transferrin; D003024:Clozapine