کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9008267 1122744 2005 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The negative immunoregulatory effects of fluoxetine in relation to the cAMP-dependent PKA pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
The negative immunoregulatory effects of fluoxetine in relation to the cAMP-dependent PKA pathway
چکیده انگلیسی
Recently, we have shown that various types of antidepressants, including selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, have negative immunoregulatory effects. These antidepressants suppress the interferon-γ (IFN-γ)/interleukin-10 (IL-10) production ratio, which is of critical importance for the determination of the capacity of immunocytes to inhibit or activate monocytic/lymphocytic functions. Since cyclic adenosine monophosphate (cAMP) production is stimulated by some antidepressants, and since cAMP inhibits IFN-γ and stimulates IL-10 production, we postulate that the negative immunoregulatory effects of antidepressants result from their effects on the cAMP-dependent protein kinase A (PKA) pathway. The aim of the present study was to determine whether the negative immunoregulatory effects of fluoxetine may be blocked by antagonists of the cAMP-dependent PKA pathway, such as, e.g., SQ 22536, an adenylate cyclase inhibitor, and Rp-8-Br-cAMPs (Rp-isomer of 8-bromo-adenosine-3′,5′-monophosphorothioate), a PKA antagonist. To this end, diluted whole blood collected from 17 normal volunteers was incubated with fluoxetine (10−6 and 10−5 M), with or without SQ 22536 (10−6 and 10−4 M) and Rp-8-Br-cAMPs (10−6 and 10−4 M), afterwards, IFN-γ, IL-10 and the tumor necrosis factor α (TNF-α) were determined. Fluoxetine, 10−6 and 10−5 M, significantly reduced the production of IFN-γ and TNF-α, and significantly decreased the IFN-γ/IL-10 production ratio. SQ 22536 and Rp-8-Br-cAMPs were unable to block the suppressant effects of fluoxetine on the IFN-γ/IL-10 ratio. Rp-8-Br-cAMPs, 10−4, but not 10−6 M, normalized the fluoxetine-induced suppression of TNF-α production. It is concluded that the suppressant effect of fluoxetine on the IFN-γ/IL-10 production ratio is probably not related to the induction of the cAMP-dependent PKA pathway, whereas the suppressant effect on TNF-α may be related to the induction of PKA. The obtained results suggest that increased activation of the PKA-dependent pathway may constitute an important molecular basis for some (suppression of TNF-α production), but not all (suppression of IFN-γ production), negative immunoregulatory effects of fluoxetine.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 5, Issue 3, March 2005, Pages 609-618
نویسندگان
, , , , , ,