Clinical application and evaluation of anti-TNF-alpha agents for the treatment of rheumatoid arthritis

Jin, Juan; Cao, Yan; Wei, Wei

doi:10.1038/aps.2010.134

Cited by 43 publications

(32 citation statements)

References 68 publications

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“…These findings suggest that therapeutic intervention aimed at reducing TNF-␣ may be beneficial for reducing immune activation during HIV infection. Indeed, TNF-␣ inhibitors have been utilized for the treatment of inflammatory conditions in HIV-infected patients (15,23,35,44). However, none of the studies performed to date has measured indicators of immune activation or monocyte function following treatment.…”

Section: Discussionmentioning

confidence: 99%

Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys

Mir

Bosinger

Gasper

et al. 2012

J Virol

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g Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent viral replication in the context of CD4؉ T cell depletion and elevated immune activation associated with disease progression. In contrast, simian immunodeficiency virus (SIV) infection of African-origin sooty mangabeys (SM) generally does not result in simian AIDS despite high viral loads and therefore affords a unique model in which to study the immunologic contributions to a nonpathogenic lentiviral disease outcome. A key feature of these natural SIV infections is the maintenance of low levels of immune activation during chronic infection. Our goal was to delineate the contribution of monocytes to maintaining low levels of immune activation in SIV-infected SM. Utilizing an ex vivo whole-blood assay, proinflammatory cytokine production was quantified in monocytes in response to multiple Toll-like receptor (TLR) ligands and a specific, significant reduction in the tumor necrosis factor alpha (TNF-␣) response to lipopolysaccharide (LPS) was observed in SIV-infected SM. In contrast, monocytes from hosts of pathogenic infections (HIV-infected humans and SIV-infected Asian macaques) maintained a robust TNF-␣ response. In SIV-infected SM, monocyte TNF-␣ responses to low levels of LPS could be augmented by the presence of plasma from uninfected control animals. The impact of LPS-induced TNF-␣ production on immune activation was demonstrated in vitro, as TNF-␣ blocking antibodies inhibited downstream CD8؉ T cell activation in a dose-dependent manner. These data demonstrate an association between nonpathogenic SIV infection of SM and a reduced monocyte TNF-␣ response to LPS, and they identify a role for monocytes in contributing to the suppressed chronic immune activation observed in these natural hosts.

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Section: Discussionmentioning

confidence: 99%

Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys

Mir

Bosinger

Gasper

et al. 2012

J Virol

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“…Multiple anti-TNF-a drugs have been licensed, 40 and anti-IL-12 antibody (ustekinumab) has been approved for treating plaque psoriasis. 41 Similarly, TNF-a 42 and IL-12 43 cytokines have been used for treatment of various cancers.…”

Section: Treg Proliferationmentioning

confidence: 99%

Differential control of Helios+/− Treg development by monocyte subsets through disparate inflammatory cytokines

Zhong

Yazdanbakhsh

2013

Blood

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“…While inflammation and remyelination are distinct processes, they are each regulated by master cytokines, such as tumor necrosis factor (TNF-α), that differentially impact infiltrating immune cells and repair of myelin injury. Thus, while successful targeting of TNF-α has led to effective treatments for peripheral autoimmune diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease [24, 27, 40], targeting TNF-α in MS patients via administration of a recombinant TNF receptor p55 immunoglobulin fusion protein (lenercept) increased frequency, duration, and severity of MS exacerbations [21], revealing critical roles for this molecule in recovery.…”

Section: Introductionmentioning

confidence: 99%

Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS

et al. 2012

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Multiple sclerosis (MS) is characterized by episodes of inflammatory demyelination with progressive failure of remyelination. Prior studies using murine models of MS indicate that remyelination within the adult central nervous system (CNS) requires the expression and activity of TNFR2 and CXCR4 by oligodendrocyte progenitor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes. Here, we extend these studies by examining the role of TNFR2 in the expression of the CXCR4 ligand, CXCL12, within the corpus callosum (CC) during cuprizone (CPZ) intoxication and by demonstrating that lentiviral-mediated gene delivery of CXCL12 to the demyelinated CC improves OPC proliferation and myelin expression during remyelination. Activated astrocytes and microglia express both TNFR1 and TNFR2 within the demyelinated CC. However, CPZ intoxicated TNFR2−/− mice exhibit loss of up-regulation of CXCL12 in astrocytes with concomitant decreases in numbers of CXCR4+ NG2+ OPCs within the CC. While CXCR4 antagonism does not affect OPC migration from subventricular zones into the CC, it decreases their proliferation and differentiation within the CC. Stereotactic delivery of lentivirus expressing CXCL12 protein into the CC of acutely demyelinated TNFR2−/− mice increases OPC proliferation and expression of myelin. In contrast, chronically demyelinated wild-type mice, which exhibit significant loss of astrocytes and OPCs, are unable to be rescued via CXCL12 lentivirus alone but instead required engraftment of CXCL12-expressing astrocytes for increased myelin expression. Our results show that TNFR2 activation induces CXCL12 expression in the demyelinated CC via autocrine signaling specifically within astrocytes, which promotes OPC proliferation and differentiation. In addition, gene delivery of critical pro-myelinating proteins might be a feasible approach for the treatment of remyelination failure in MS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-012-1034-0) contains supplementary material, which is available to authorized users.

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Clinical application and evaluation of anti-TNF-alpha agents for the treatment of rheumatoid arthritis

Cited by 43 publications

References 68 publications

Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys

Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation in Sooty Mangabeys

Differential control of Helios+/− Treg development by monocyte subsets through disparate inflammatory cytokines

Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS

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