Effects of atypical antipsychotics on the inflammatory response system in schizophrenic patients resistant to treatment with typical neuroleptics

There is now some evidence that schizophrenia may be accompanied by an acti vation of the inflammatory response system (IRS) and that typical antipsych otics may suppress some signs of IRS activation in that illness. This study was carried out to examine (i) the serum concentrations of interleukin-6 ( IL-6), IL-6 receptor (IL-6R), IL-1R antagonist (IL-1RA) and Clara Cell prot ein (CC16), an endogenous anticytokine, in nonresponders to treatment with typical neuroleptics and (ii) the effects of atypical antipsychotics on the above IRS variables. The above parameters were determined in 17 patients w ith treatment-resistant schizophrenia (TRS) to treatment with neuroleptics and in seven normal volunteers and 14 schizophrenic patients who had a good response to treatment with antipsychotic agents. Patients with TRS had rep eated measurements of the IRS variables before and 2 and 4 months after tre atment with atypical antipsychotics. Serum IL-6 was significantly higher in schizophrenic patients, irrespective of their response to typical antipsyc hotics, than in normal controls. Serum IL-IRA was significantly higher in t he TRS patients than in controls, whereas responders took up an intermediat e position. The serum concentrations of CC16 were significantly lower after treatment with atypical antipsychotics during 4 months than before treatme nt. It is concluded that iii schizophrenia and, in particular, TRS is chara cterized by an activation of the monocytic arm of cell-mediated immunity an d (ii) atypical antipsychotics may decrease the anti-inflammatory capacity of the serum in TRS patients. (C) 2000 Elsevier Science B.V. All rights res erved.