Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells

Immunopharmacology. 1996 Aug;34(1):27-37. doi: 10.1016/0162-3109(96)00111-7.

Abstract

Tricyclic antidepressants (TCAs) are widely used in treating depressive disorders. It has been demonstrated that, for instance, IL-1 beta and IL-6 inhibit the HPA axis, which plays a role in the development of depressions. Therefore. we were interested in investigating how TCAs influence cytokine release by T lymphocytes and monocytes respectively. Cells were incubated with either 5 microM clomipramine, 15 microM imipramine or 20 microM citalopram. IL-2 release was suppressed to 60% of the control values by clomipramine and imipramine (p = 0.001; p = 0.000), but citalopram was found to cause a much weaker inhibition (only 18%) (p = 0.16). INF-gamma release was affected to a lower degree than IL-2 release, and imipramine (34%) (p = 0.054) was more potent than clomipramine (24%) (p = 0.16) and citalopram (12%) (p = 0.059) in this case. Monocytes incubated with TCA for 4 h exhibited only limited inhibition of IL-1 beta and IL-6 release, i.e., 6-25% for all three compounds. The corresponding value for TNF-alpha release was 20-45% inhibition, with citalopram being the weakest inhibitor. After 10 h of monocytes to LPS exposure, all three compounds exerted a strong inhibition of IL-1 beta and TNF-alpha release, i.e., 60-70% with p-values below 0.012 for all of them. However the inhibition of IL-6 release was less than 35%. Citalopram was equality as potent as imipramine and clomipramine in inhibiting IL-6 release after long-term exposure of monocytes to LPS. All three TCAs elevated intracellular cAMP concentrations significantly in T lymphocytes and monocytes (p < 0.001).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents, Tricyclic / pharmacology*
  • Cyclic AMP / metabolism
  • Cytokines / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-6 / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism*
  • Lymphocyte Activation / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antidepressive Agents, Tricyclic
  • Cytokines
  • Interleukin-1
  • Interleukin-2
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Cyclic AMP