Modulation of serotonin transporter function by interleukin-4

doi:10.1016/S0024-3205(00)00992-9

Life Sciences

Volume 68, Issue 8, 12 January 2001, Pages 873-880

https://doi.org/10.1016/S0024-3205(00)00992-9 Get rights and content

Abstract

Serotonin (5-HT) is an important mediator of interactions between the nervous and immune systems. 5-HT signaling is regulated by the 5-HT transporter (5-HTT), which determines the magnitude and duration of serotonergic responses. Due to this important role, regulation of the 5-HTT by cytokines has been the focus of recent interest. A number of proinflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interferon-γ, have been shown to upregulate the 5-HTT. In the present study we investigated the influence of interleukin-4 (IL-4), which acts as an anti-inflammatory cytokine in the central nervous system, on the 5-HTT. As a model system we used immortalized B lymphocytes, which not only express the 5-HTT, but also allow testing the co-modulatory influence of a recently described polymorphism in the 5-HTT gene promoter (5-HTTLPR) that is associated with anxiety- and depression-related behavioral traits. The results show that IL-4 induces a dose-dependent reduction of 5-HT uptake. This effect is preferentially seen in cell lines homozygous for the long, high-activity allele of the 5-HTTLPR. In conclusion, a picture of differential modulation of the 5-HTT by proinflammatory and anti-inflammatory cytokines is emerging, which may represent a fine-tuned mechanism to communicate the state of an immune response to the central nervous system.

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Original articlesModulation of serotonin transporter function by interleukin-4

Abstract

Original articles
Modulation of serotonin transporter function by interleukin-4