The Interleukin-10 Family of Cytokines and Their Role in the CNS

Abstract

Resident cells of the central nervous system (CNS) play an important role in detecting insults and initiating protective or sometimes detrimental host immunity. At peripheral sites, immune responses follow a biphasic course with the rapid, but transient, production of inflammatory mediators giving way to the delayed release of factors that promote resolution and repair. Within the CNS, it is well known that glial cells contribute to the onset and progression of neuroinflammation, but it is only now becoming apparent that microglia and astrocytes also play an important role in producing and responding to immunosuppressive factors that serve to limit the detrimental effects of such responses. Interleukin-10 (IL-10) is generally considered to be the quintessential immunosuppressive cytokine, and its ability to resolve inflammation and promote wound repair at peripheral sites is well documented. In the present review article, we discuss the evidence for the production of IL-10 by glia, and describe the ability of CNS cells, including microglia and astrocytes, to respond to this suppressive factor. Furthermore, we review the literature for the expression of other members of the IL-10 cytokine family, IL-19, IL-20, IL-22 and IL-24, within the brain, and discuss the evidence of a role for these poorly understood cytokines in the regulation of infectious and sterile neuroinflammation. In concert, the available data indicate that glia can produce IL-10 and the related cytokines IL-19 and IL-24 in a delayed manner, and these cytokines can limit glial inflammatory responses and/or provide protection against CNS insult. However, the roles of other IL-10 family members within the CNS remain unclear, with IL-20 appearing to act as a pro-inflammatory factor, while IL-22 may play a protective role in some instances and a detrimental role in others, perhaps reflecting the pleiotropic nature of this cytokine family. What is clear is that our current understanding of the role of IL-10 and related cytokines within the CNS is limited at best, and further research is required to define the actions of this understudied family in inflammatory brain disorders.

Suppressors of Cytokine Signaling (SOCS)1 and SOCS3 Proteins Are Mediators of Interleukin-10 Modulation of Inflammatory Responses Induced byChlamydia muridarumand Its Major Outer Membrane Protein (MOMP) in Mouse J774 Macrophages

“…Herein, the potent IL-10 anti-inflammatory function [31,93,94] is now validated for chlamydial inflammation by impeding the release of not only cytokines but also chemokines in macrophages, which are congruent with our previous findings [27,41]. Many investigators have reported on IL-10 inhibitory actions in macrophages exposed to protozoans (Leishmania braziliensis and Leishmania chagasi), viruses (Tacaribe Virus), fungal and bacteria (Chlamydia spp., Borrelia burgdorferi, Helicobacter pylori, Staphylococcus aureus, Streptococcus pneumoniae, and Yersinia enterocolitica) [95].…”

Stimulus‐dependent modifications in astrocyte‐derived extracellular vesicle cargo regulate neuronal excitability

“…ATP levels are extremely high in supernatants collected from HIV‐infected patients and IL‐1β concentrations are elevated in the CNS of several CNS disorders including Parkinson's Disease, Alzheimer's Disease, HIV‐associated neurocognitive disorders (Festa, Gutoskey, Graziano, Waterhouse, & Meucci, ; Griffin et al, ; Mogi et al, ), and IL‐10 plays a critical role in limiting neuroinflammation (Burmeister & Marriott, ). Particularly in HIV‐associated neurocognitive disorders the ratio of IL‐1β to IL‐10 is correlated to brain atrophy (Kallianpur, ).…”

“…Bonferroni correction was applied to correct for multiple comparisons. Disease, HIV-associated neurocognitive disorders (Festa, Gutoskey, Graziano, Waterhouse, & Meucci, 2015;Griffin et al, 1989;Mogi et al, 1994), and IL-10 plays a critical role in limiting neuroinflammation (Burmeister & Marriott, 2018). Particularly in HIV-associated neurocognitive disorders the ratio of IL-1β to IL-10 is correlated to brain atrophy (Kallianpur, 2014).…”

Through Reducing ROS Production, IL-10 Suppresses Caspase-1-Dependent IL-1β Maturation, thereby Preventing Chronic Neuroinflammation and Neurodegeneration

“…Thus, both in vivo and in vitro findings indicated that IL-10 downregulated NLRP3, caspase-1, and IL-1β (Figure 1a-c). No significant difference in mRNA levels of NLRP3, caspase-1, and IL-1β between WT and IL-10 −/− microglia-enriched cultures after LPS treatment ( Figure 1c) was due to delayed IL-10 production in WT microglial culture system after LPS treatment [17][18][19][20]. In other words, delayed production of IL-10 in WT microglial cultures made IL-10 miss the window to affect gene transcription and mRNA degradation of these genes, which happened earlier.…”