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Interleukin‐10 attenuates production of HSV‐induced inflammatory mediators by human microglia
Author(s) -
Marques Cristina P.,
Hu Shuxian,
Sheng Wen,
Cheeran Maxim CJ.,
Cox Diana,
Lokensgard James R.
Publication year - 2004
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20045
Subject(s) - microglia , cxcl10 , ccl5 , biology , chemokine , cytokine , immunology , immune system , tumor necrosis factor alpha , inflammation , herpes simplex virus , interleukin 10 , interleukin , t cell , virus , il 2 receptor
Infection of the central nervous system (CNS) with herpes simplex virus (HSV)‐1 initiates a rapidly progressive, necrotizing, and fatal encephalitis in humans. Even with the advent of antiviral therapy, effective treatments for HSV‐1 brain infection are limited because the cause of the resulting neuropathogenesis is not completely understood. We previously reported that human microglial cells, while nonproductively infected, respond to HSV‐1 by producing robust amounts of pro‐inflammatory mediators, such as tumor necrosis factor(TNF), interleukin (IL)‐1β, CCL5 (RANTES), and CXCL10 (IP‐10). Although initiation of immune responses by glial cells is an important protective mechanism in the CNS, unrestrained inflammatory responses may result in irreparable brain damage. To elucidate the potential immunomodulatory role of anti‐inflammatory cytokines, we investigated the effects of IL‐4, IL‐10, and transforming growth factor (TGF)‐β on microglial cell cytokine and chemokine production in response to HSV‐1. Results from these studies demonstrated a consistent IL‐10‐mediated suppression of TNF‐α (60% ± 2%), IL‐1β (68% ± 3%), CCL5 (62 ± 4%), but not CXCL10 production by HSV‐1‐infected microglial cells. This inhibition was associated with decreased HSV‐1‐induced activation of NF‐κB. These results suggest that IL‐10 has the ability to regulate microglial cell production of immune mediators and thereby, dampen the pro‐inflammatory response to HSV‐1. © 2004 Wiley‐Liss, Inc.