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The role of CCR1 and therapeutic effects of anti-CCL3 antibody in herpes simplex virus-induced Behcet's disease mouse model.

ABSTRACT: Behçet's disease (BD) is a chronic systemic inflammatory disease with unclear etiopathogenesis. Although gene variants of CC chemokine receptor type 1 (CCR1) have been reported, the protein expression of CCR1 in patients with BD remains unclear. The objective of this study was to analyze the frequencies of CCR1+ cells in a herpes simplex virus-induced mouse model of BD. The frequencies of CCR1+ cells on the surface and in the cytoplasm of peripheral blood mononuclear cells and lymph nodes were analyzed by flow cytometry. The CCR1+ cells were significantly down-regulated in BD mice compared with the normal control and symptom-free control mice. Colchicine and pentoxifylline treatment improved the symptoms of BD and increased the frequencies of CCR1+ cells in BD mice. Treatment with chemokine CC motif ligand 3 (CCL3), a ligand of CCR1, caused BD symptoms to deteriorate in 10 of 16 BD mice (62·5%) via down-regulation of CCR1+ cells. Anti-CCL3 antibody treatment ameliorated BD symptoms in 10 of 20 mice (50%) and significantly decreased the disease severity score compared with CCL3-treated BD mice (P = 0·01) via up-regulation of CCR1+ cell frequencies. In patients with BD, plasma levels of CCL3 in an active state were significantly higher than in healthy control individuals (P = 0·02). These results show that the up-regulation of CCR1+ cells was related to the control of systemic inflammation of BD in mouse models.

SUBMITTER: Sayeed HM

PROVIDER: S-EPMC6797864 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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The role of CCR1 and therapeutic effects of anti-CCL3 antibody in herpes simplex virus-induced Behçet's disease mouse model.

Sayeed Hasan M HM Lee Eun-So ES Byun Hae-Ok HO Sohn Seonghyang S

Immunology 20190908 3

Behçet's disease (BD) is a chronic systemic inflammatory disease with unclear etiopathogenesis. Although gene variants of CC chemokine receptor type 1 (CCR1) have been reported, the protein expression of CCR1 in patients with BD remains unclear. The objective of this study was to analyze the frequencies of CCR1<sup>+</sup> cells in a herpes simplex virus-induced mouse model of BD. The frequencies of CCR1<sup>+</sup> cells on the surface and in the cytoplasm of peripheral blood mononuclear cells ...[more]

PMID: 31393598

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Project description:BACKGROUND:Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis. OBJECTIVES:To compare the relative effectiveness of antiviral agents, interferon, and corneal débridement in the treatment of acute HSV epithelial keratitis. SEARCH STRATEGY:We searched CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (January 1950 to October 2010), EMBASE (January 1980 to October 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2010), Zetoc (British Library's Electronic Table of Contents), System for Information on Grey Literature in Europe (openSIGLE), Biosciences Information Service (BIOSIS), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), Japan Information Center of Science and Technology (JICST-EPlus), and China Academic Journals database (CAJ) via China National Knowledge Infrastructure (CNKI) with citations confirmed using China/Asia On Demand (COAD). There were no language or date restrictions in the search for trials. All databases except CNKI and COAD were last searched on 27 October 2010, CNKI and COAD were searched on 1 April 2010. We also searched literature digests, conference proceedings and reference lists. SELECTION CRITERIA:Of 152 eligible studies,106 comparative treatment trials involving 5872 eyes with dendritic or geographic epithelial keratitis were analysed for corneal healing over two weeks. DATA COLLECTION AND ANALYSIS:Interventions were compared at 14 days after trial enrolment by calculating a risk ratio (RR) that was adjusted with indirect RR, assessed by an inconsistency index (I(2) ) and supplemented by a seven-day RR and a hazard ratio (HR). MAIN RESULTS:Idoxuridine, though uncertainly better in healing outcome than control because of few trials with 14-day follow up, allowed earlier corneal re-epithelialisation. Vidarabine resulted in a significantly better outcome than placebo in one trial (RR 1.96; 95% CI 1.10 to 3.49). Compared to idoxuridine, in combined direct and indirect analyses, vidarabine (RR 1.11; 95% CI 1.03 to 1.19), trifluridine (RR 1.31; 95% CI 1.20 to 1.42), acyclovir (RR 1.23; 95% CI 1.16 to 1.31), brivudine (RR 1.38; 95% CI 1.18 to 1.61), and ganciclovir (RR 1.40; 95% CI 1.25 to 1.57) were significantly more effective. Trifluridine (RR 1.12; 95% CI 1.04 to 1.21) and acyclovir (RR 1.11; 95% CI 1.05 to 1.19) appeared more effective than vidarabine. No significant differences were found in comparisons between acyclovir, trifluridine and brivudine. The comparison of ganciclovir to acyclovir was limited by heterogeneity and possible publication bias. The joint use of two topical antivirals (RR 1.00; 95% CI 0.89 to 1.12) and the use of oral acyclovir alone (RR 0.92; 95% CI 0.79 to 1.07) or combined with a topical antiviral (RR 1.08; 95% CI 0.99 to 1.17) appeared as effective as topical antiviral therapy. Compared to antiviral monotherapy, the combination of an antiviral with interferon (RR 1.03; 95% CI 0.99 to 1.07) or with débridement (RR 1.04; 95% CI 0.95 to 1.14) did not yield significantly better outcomes but may have accelerated healing. The corneal epithelial healing outcome was improved when antiviral therapy was added to débridement (RR 1.21; 95% CI 1.04 to 1.42). AUTHORS' CONCLUSIONS:Trifluridine and acyclovir are more effective than idoxuridine or vidarabine, and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.

Dataset Information

The role of CCR1 and therapeutic effects of anti-CCL3 antibody in herpes simplex virus-induced Behcet's disease mouse model.

Publications

The role of CCR1 and therapeutic effects of anti-CCL3 antibody in herpes simplex virus-induced Behçet's disease mouse model.

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