Brodalumab: A Review in Moderate to Severe Plaque Psoriasis

Blair, Hannah A.

doi:10.1007/s40265-018-0888-4

Cited by 24 publications

(19 citation statements)

References 21 publications

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“…IL-17 blockers have been developed for treating inflammatory diseases, such as psoriasis and arthritis (Kivelevitch and Menter, 2015). Brodalumab (Kyntheum) is a human anti-interleukin-17 receptor A (IL-17RA) monoclonal antibody available for use in patients with moderate to severe plaque psoriasis (Blair, 2018). Because mouse IL-17RA antibody is effective in suppressing neuronal hyperexcitability after paclitaxel, brodalumab could be used to treat CIPN and neuropathic pain.…”

Section: Modulation Of Inhibitory Synaptic Transmission By Il-17 and Il-17rmentioning

confidence: 99%

Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy

Luo¹,

Liu²,

Zhang³

et al. 2019

Cell Reports

102

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The proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here, we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in the spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We find that IL-17 not only enhances excitatory postsynaptic currents (EPSCs) but also suppresses inhibitory postsynaptic synaptic currents (IPSCs) and GABAinduced currents in lamina II o somatostatin-expressing neurons in mouse spinal cord slices. IL-17 mainly expresses in spinal cord astrocytes, and its receptor IL-17R is detected in somatostatin-expressing neurons. Selective knockdown of IL-17R in spinal somatostatin-expressing interneurons reduces paclitaxel-induced hypersensitivity. Overexpression of IL-17 in spinal astrocytes is sufficient to induce mechanical allodynia in naive animals. In dorsal root ganglia, IL-17R expression in nociceptive sensory neurons is sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate neuron-glial interactions and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy.

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Section: Modulation Of Inhibitory Synaptic Transmission By Il-17 and Il-17rmentioning

confidence: 99%

Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy

Luo¹,

Liu²,

Zhang³

et al. 2019

Cell Reports

102

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show abstract

“…These three cytokines are efficient targets in the treatment of psoriasis in clinic. For example, Brodalumab is the anti-IL17RA antibody and has been approved for use in patients with moderate to severe plaque psoriasis 37 . About 40% of patients receiving 12 week of induction therapy with subcutaneous brodalumab achieve a complete skin clearance (PASI 100).…”

Section: Discussionmentioning

confidence: 99%

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration

Gou

et al. 2021

Cell Death Dis

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Psoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.

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“…IL-17 blockers have been developed for treating inflammatory diseases such as psoriasis and arthritis (Kivelevitch and Menter, 2015). Brodalumab (Kyntheum®) is a human anti-interleukin-17 receptor A (IL-17RA) monoclonal antibody available for use in patients with moderate to severe plaque psoriasis (Blair, 2018). Since mouse IL-17RA antibody is effective in suppressing neuronal hyperexcitability after paclitaxel, Brodalumab could be used to treat CIPN and neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-17 regulates neuron-glial communications, inhibitory synaptic transmission and neuropathic pain after chemotherapy

Luo

Liu

Luo

et al. 2018

Preprint

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Brodalumab: A Review in Moderate to Severe Plaque Psoriasis

Cited by 24 publications

References 21 publications

Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy

Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration

Interleukin-17 regulates neuron-glial communications, inhibitory synaptic transmission and neuropathic pain after chemotherapy

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