IL-1R Antagonist

IL-1R Antagonist (TLR1) is a peptide that mimics the primary response gene 88 (MyD88) of myeloid differentiation and can alter the interaction between MyD88 and IL-1 receptor type I (IL-1RI)^[1]. Treatment of mouse lymphocytes and thymoma EL4 cells with IL-1R Antagonist (>=10μM) can inhibit the phosphorylation of IL-1β-activated p38 MAP kinase, a process specifically mediated by the disruption of IL-1RI/MyD88^[1]. IL-1R Antagonist can block the stress-like effects of IL-1β in cellular and behavioral models and has the potential to be a new candidate drug for the treatment of depression^[2]. IL-1R Antagonist can effectively inhibit the activation of JNK (c-Jun N-terminal kinase) and NF-κB (nuclear factor κB) pathways^[3].

In vivo, IL-1R Antagonist (200mg/kg) administered via intraperitoneal injection to mice with IL-1β-induced fever significantly reduced the IL-1β-induced fever response^[1].

References:
[1] Bartfai T, Behrens M M, Gaidarova S, et al. A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits IL-1 receptor-mediated responses[J]. Proceedings of the National Academy of Sciences, 2003, 100(13): 7971-7976.
[2] Koo J W, Duman R S. Evidence for IL-1 receptor blockade as a therapeutic strategy for the treatment of depression[J]. Current opinion in investigational drugs (London, England: 2000), 2009, 10(7): 664.
[3] Loiarro M, Ruggiero V, Sette C. Targeting TLR/IL‐1R signalling in human diseases[J]. Mediators of inflammation, 2010, 2010(1): 674363.

IL-1R Antagonist（TLR1）是一种模拟髓系分化初级反应基因88（MyD88）的肽，能够改变MyD88和IL-1受体类型I（IL-1RI）的相互作用^[1]。IL-1R Antagonist（>=10μM）处理小鼠淋巴细胞和胸腺瘤EL4细胞，能够抑制IL-1β激活的p38 MAP激酶磷酸化，这一过程是由IL-1RI/MyD88的破坏特异性介导的^[1]。IL-1R Antagonist可以阻断IL-1β在细胞和行为模型中的应激样效应，具有作为治疗抑郁症新候选药物的潜力^[2]。IL-1R Antagonist能够有效抑制JNK（c-Jun N-terminal kinase）和NF-κB（nuclear factor κB）通路的激活^[3]。

在体内，IL-1R Antagonist（200mg/kg）通过腹腔注射治疗IL-1β诱导发热的小鼠，显著减弱了IL-1β诱导的发热反应^[1]。