In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: Effect of glucocorticoid therapy

Belguendouz, Houda; Messaoudene, D.; Lahmar-Belguendouz, K.; Djeraba, Zineb; Otmani, F.; Terahi, Malika; Tiar, M.; Hartani, D.; Lahlou-Boukoffa, Ouidad; Touil-Boukoffa, Chafia

doi:10.1016/j.jfo.2014.10.005

Cited by 12 publications

(7 citation statements)

References 39 publications

(39 reference statements)

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“…1 The primary basis for recurrent uveitis IL-18 is a cytokine that belongs to the IL-1 super-family and is an inflammatory factor in many diseases. 31,36,[52][53][54] Increases in intraocular levels of IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8 and MCP-1 have all been found to be associated with uveitis. 55,56 However, the mechanisms of IL-18 as related to uveitis remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…The nuclear factor (NF) kappa-light-chain-enhancer of activated B cells (κB) and mitogen-activated protein kinase pathways (MAPK pathways) are then activated, which promote IFN-γ transcription and stabilization of IFNG mRNA. [26][27][28] Recently, the role of IL-18 in uveitis has attracted considerable attention as it has been shown in both clinical and EAU models, that IL-18 shows enhanced expression during the inflammatory phase of the disease, [29][30][31][32][33][34] and polymorphism of the IL-18 gene is closely related to the occurrence of uveitis. 35,36 Thus, these reports indicate that IL-18 might participate in the inflammation of EAU.…”

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confidence: 99%

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CD83⁺CCR7⁺ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

Man

Wang

et al. 2018

J Cellular Molecular Medi

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Natural killer (NK) cells have been reported to play a pathological role in autoimmune uveitis. However, the mechanisms regarding NK cells in uveitis and factors that affect NK‐cell activation in this condition remain unclear. Here, we report that the number of CD3 ‐ NK1.1 + CD83 + CCR7 + cells is increased in the inflamed eyes within a mouse model of experimental autoimmune uveitis (EAU), and these cells express elevated levels of NKG2D, CD69 and IFN‐γ. Adoptively transferring CD83 + CCR7 + NK cells aggravates EAU symptoms and increases the number of CD4 + IFN‐γ + T cells and dendritic cells (DCs) within the eye. These CD83 + CCR7 + NK cells then promote the maturation of DCs and IFN‐γ expression within T cells as demonstrated in vitro. Furthermore, IL‐18, as primarily secreted by DCs in the eyes, is detected to induce CD83 + CCR7 + NK cells. In EAU mice, anti‐IL‐18R antibody treatment also decreases retinal tissue damage, as well as the number of infiltrating CD83 + CCR7 + NK cells, T cells and DCs in the inflamed eyes and spleens of EAU mice. These results suggest that CD83 + CCR7 + NK cells, as induced by IL‐18 that primarily secreted by DCs, play a critical pathological role in EAU. Anti‐IL‐18R antibody might serve as a potential therapeutic agent for uveitis through its capacity to inhibit CD83 + CCR7 + NK cells infiltration.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

CD83⁺CCR7⁺ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

Man

Wang

et al. 2018

J Cellular Molecular Medi

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“…Moreover, IL17 and IL18 were related to uveitis in BD, and IL8, RANTES and MIP-1α were associated with disease activity. 6 Although corticosteroids in combination with conventional immunosuppressive agents Effectiveness and safety of interferon α2a as an add-on treatment for refractory Behçet's uveitis such as cyclosporin A (CsA) and azathioprine (AZA) remain the mainstay of the treatment in BD patients with uveitis, a moderate proportion of patients respond inadequately to the above agents even at their maximum therapeutic doses, and some experience intolerable side effects. Therefore, there is an urgent need for additional effective treatments to combat this disease.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness and safety of interferon α2a as an add-on treatment for refractory Behçet’s uveitis

Shi

Zhao

Zhou

et al. 2019

Therapeutic Advances in Chronic Disease

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Objective: The objective of this study was to investigate the effectiveness and safety of interferon (IFN) α2a as an add-on treatment for refractory Behçet’s uveitis (BU). Methods: In this retrospective cohort study, 30 refractory BU patients who received IFNα2a treatment in Peking Union Medical College Hospital between February 2015 and June 2018 were consecutively included. IFNα2a was used mainly as an add-on treatment for BU patients who underwent relapse under corticosteroids and conventional immunosuppressive agents. The primary outcome was treatment success rate before and after initiation of IFNα2a. Changes in ocular relapse rates, disease activity, corticosteroid- and immunosuppressant-sparing effects, as well as side effects were secondary outcomes. Results: A total of 30 patients (27 males and 3 females) with a mean age of 30.5 ± 8.7 years were included. Twenty-one patients (70%) were treated with at least 2 immunosuppressive agents before the initiation of IFNα2a. Treatment success was achieved in 26 patients (86.7%), and the median uveitis relapse rate decreased from 7.3 (range 2–12) to 0 (range 0–6) per patient-year ( p = 0.000002) during a mean follow-up of 21.7 ± 7.5 months, corticosteroids were lowered in 25 cases (83.3%) and completely withdrawn in four (13.3%). In addition, immunosuppressive agents were reduced in number and dosage in 22 (73.3%) and 29 patients (96.7%), respectively, and were completely withdrawn in 12 cases (40%). No severe adverse events were observed and serum autoantibodies remained negative during the treatment of IFNα2a. Conclusion: IFNα2a is effective and relatively safe in refractory BU, with significant steroid- and immunosuppressant-sparing effects.

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“…Autoantibodies, binding molecules exposed on the surface of neurons, lead to a neurotoxic effect [1,30]. Increased levels of TNF, IL-6 [31], IL-18 [32] and IL-8 have been reported in cultures of monocytes from people with BD [33,34]. IL-8 in particular attracts and activates neutrophils and other leukocytes and is thought to mediate endothelial damage in BD.…”

Section: Discussionmentioning

confidence: 99%

The role of infections in Behçet disease and neuro-Behçet syndrome

Marta¹,

Santos²,

Coutinho³

et al. 2015

Autoimmunity Reviews

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Infections are considered an environmental trigger for exacerbations of immune-mediated diseases. We aimed to establish if common viral infections could be identified as a precipitant of Behçet disease (BD) with or without neurological involvement and to assess the variability of the immune response to common viruses. We also investigated whether cytokines and chemokines could be markers of neurological involvement. Finally, we explored if anti-basal ganglia antibodies (ABGAs) would be associated with neurological involvement in BD. Our study included 14 individuals with BD with neurological involvement (neuroBehçet syndrome - NBS), 16 individuals with BD without neurological involvement and 18 healthy controls (HC). Overall we found a tendency for increased levels of anti-viral IgG antibody levels in BD, more evident in NBS patients versus HC. Epstein-Barr viral-capsid antigen IgG titres were increased in NBS patients versus other BD patients (p=0.032). Anti-measles antibody titres induced by vaccination were similarly elevated. ABGAs were not detected in the serum of our cohort. Raised levels of serum IL-8 in some BD patients did not reflect clinical activity or severity. In conclusion, there was evidence for a polyclonal immune activation rather than a specific virus effect in the sera of individuals with BD or NBS.

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In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: Effect of glucocorticoid therapy

Cited by 12 publications

References 39 publications

CD83⁺CCR7⁺ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

CD83⁺CCR7⁺ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

Effectiveness and safety of interferon α2a as an add-on treatment for refractory Behçet’s uveitis

The role of infections in Behçet disease and neuro-Behçet syndrome

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In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: Effect of glucocorticoid therapy

Cited by 12 publications

References 39 publications

CD83+CCR7+ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

CD83+CCR7+ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

Effectiveness and safety of interferon α2a as an add-on treatment for refractory Behçet’s uveitis

The role of infections in Behçet disease and neuro-Behçet syndrome

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CD83⁺CCR7⁺ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis

CD83⁺CCR7⁺ NK cells induced by interleukin 18 by dendritic cells promote experimental autoimmune uveitis