These drugs reduced the IFN-γ production significantly, while sertraline and clomipramine additionally raised the IL-10 production.61 Regarding other in-vitro studies, a significantly reduced production of IFN-γ, IL-2, and sIL-2R was found after antidepressant treatment compared with pretreatment values.63 A I-BET151 purchase downregulation of the IL-6 production was observed during amitriptyline treatment; in treatment responders, the TNF-α production decreased
to normal.66 There are also studies, however, showing no effect of antidepressants to the in-vitro stimulation of cytokines (overview, ref 67) but methodological issues have to be taken into Inhibitors,research,lifescience,medical account. There is significant evidence suggesting that antidepressants of different classes induce downregulation of the type 1 cytokine production in vitro,67 including noradrenaline reuptake inhibitors68 Inhibitors,research,lifescience,medical and the ”dual“ serotonin and noradrenalin reuptake inhibitors.69 Several researchers have observed a reduction of IL-6 during treatment with the serotonin reuptake inhibitor fluoxetine.70 A decrease of IL-6 serum levels during therapy with different antidepressants has been observed by other researchers.71 The shift of imbalanced IFNγ/IL-4 towards normal after 6 weeks’ antidepressant
treatment has also Inhibitors,research,lifescience,medical been reported.41 On the other hand, other groups did not find any effect of Inhibitors,research,lifescience,medical some antidepressants on serum levels of different cytokines.61,72 Since IL-6
stimulates PGE2 and antidepressants inhibit IL-6 production, an inhibiting action of antidepressants on PGE2 would be expected, too.73 Over 30 years ago it was suggested that antidepressants inhibit PGE2.74 A recent invitro study showed that both tricyclic antidepressants and selective serotonin inhibitors attenuated cytokine-induced PGE2 and nitric oxide production by inflammatory cells.75 Nonpharmacological therapies: electroconvulsive Inhibitors,research,lifescience,medical therapy and sleep deprivation Electroconvulsive therapy (ECT) was found to downregulate Olopatadine increased levels of the proinflammatorycytokine TNF-α in patients with MD.76 An immune analysis during sleep showed an increase in the type-1 monocyte derived cytokines TNF-α and IL-12 and a decrease of the type-2 IL-10 producing monocytes.77 In contrary, continuous wakefulness blocked the increase of type-1 and decrease of type-2 cytokines (T. Lange and S. Dimitrov, personal communication). Thus, sleep deprivation may exert therapeutic effects through a low suppression of type-1 cytokines. Antidepressant pharmacotherapy, but also other antidepressant therapeutic agents or techniques, have a downregulating effect on proinflammatory cytokines.