ABSTRACT
Cytokine production by peripheral blood mononuclear cells (PBMC) was assessed in 10 major depressed patients (5 men and 5 women) before and after 4 weeks of clomipramine treatment and in age- and gender-matched healthy controls. A significant reduction in interleukin-1B (IL-1B), interleukin-2 (IL-2) and interleukin-3-like activity (IL-3-LA) was observed in untreated depressed patients when compared to controls. IL-1B and IL-3-LA synthesis was significantly increased after drug treatment. The suppression of cytokine production by PBMC in depressed patients may be attributed to the depression per se, or it may be related to depression-associated hyperactivity of the hypothalamic-pituitary-adrenal axis. The mode of interaction between depression and cellular immune function and the mediators responsible for the reduced cytokine production need to be studied further.
Subject(s)
Clomipramine/therapeutic use , Depressive Disorder/drug therapy , Interleukins/blood , Adult , Aged , Clomipramine/adverse effects , Depressive Disorder/immunology , Depressive Disorder/psychology , Female , Humans , Interleukin-1/blood , Interleukin-2/blood , Interleukin-3/blood , Male , Middle Aged , Monocytes/immunologyABSTRACT
The present study was designed to evaluate the inhibitory effect of antidepressants on thrombin-induced phosphoinositide (PI) hydrolysis. Thrombin 5 units/ml induced a 100%-200% increase in platelet inositol phosphates (IPs) formation. This effect was inhibited in a dose-dependent manner by various heterocyclic antidepressants (IC50 40-170 mumol/L) The monoamine oxidase inhibitor, phenelzine, in concentrations up to 500 mumol/L, was devoid of inhibitory activity. The tricyclic antidepressants, (50 mumol/L) inhibited also thrombin-induced platelet aggregation by 32%-47%. No alteration in thrombin-induced IPs formation was detected in recovered major depressed patients (n = 15) maintained on clomipramine (75-150 mg/day). These results indicate that the heterocyclic antidepressants interfere with the thrombin-linked PI-signaling system. However, the inhibitory effect is achieved only in concentrations above the plasma concentrations obtained with therapeutic doses of these agents.
