Interferon beta-1b increases interleukin-10 in a model of T cell-microglia interaction: relevance to MS.
BACKGROUND
The modes of action of interferon beta (IFN-beta) in MS remain unclear, but enhanced levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in the CSF of patients with MS may be a marker of its prognostic efficacy.


OBJECTIVE
To examine potential mechanisms by which IL-10 may be increased by IFN-ss in the milieu of the CNS.


METHODS
A model of T cell interaction with microglia in vitro was used. Production of cytokines was monitored by measuring the levels of various cytokine proteins, using ELISA.


RESULTS
Pretreatment of T cells with IFN-beta potentiates the production of IL-10 when they interact with adult human microglia, human fetal microglia, or U937 cells treated with phorbol-12-myristate-13-acetate (PMA) and IFN-gamma. The enhancing effect of IFN-beta on IL-10 requires cell-cell contact, but does not seem to depend on pathways implicated in microglia-T cell interactions, involving CD40, CD23, and B7. In contrast to IL-10, IFN-beta inhibits the production of other cytokines, including tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-4, IL-12, and IL-13.


CONCLUSIONS
The increase of IL-10 in microglia-T cell interaction by IFN-beta together with a decrease of other cytokines may lead to a noninflammatory milieu in the CNS. This mechanism could contribute to the efficacy of IFN-beta in MS.
Chabot
S
S
Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
Yong
V W
VW
D000704:Analysis of Variance; D018920:Coculture Techniques; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D016753:Interleukin-10; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a