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.