The effect of repeated amitriptyline and desipramine administration on cytokine release in C57BL/6 mice.
This study examines the effects of repeated amitriptyline and desipramine administration (10 mg/kg, IP) on the immunoreactivity of saline-injected C57BL/6 mice, as evaluated by the ability of splenocytes to reduce a tetrazolium salt to formazan (MTT test), to proliferate, and to produce cytokines, such as interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IFN-gamma). Desipramine and amitriptyline administered for one or two weeks enhance the biochemical (estimated by MTT test) and proliferative activities of splenocytes. One and two weeks administration of desipramine significantly reduces the secretion of IL-4, an anti-inflammatory cytokine. Amitriptyline administration for four weeks stimulates the proliferative activity of splenocytes and enhances IL-2 bioactivity, whereas four weeks desipramine aministration does not change these parameters in comparison to saline treated control mice. Prolonged desipramine administration (seven and 28 days) significantly increased the bioactivity of IL-1. Four weeks of prolonged administration of amitriptyline and desipramine induces a significant increase in the secretion of IL-10, a cytokine with immunosuppressive and anti-inflammatory activities. The results show that the immunoregulatory effects of tricyclic antidepressants in C57BL/6 mice depend on the drugs used and on the duration of administration.
Kubera
M
M
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343, Krakow, Poland.
Holan
V
V
Mathison
R
R
Maes
M
M
D000639:Amitriptyline / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D003891:Desipramine / Q000008:administration & dosage* / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016753:Interleukin-10; D000639:Amitriptyline; D015847:Interleukin-4; D007371:Interferon-gamma; D003891:Desipramine