Intravenous Administration of Toll-Like Receptor Inhibitory Peptide 1 is Effective for the Treatment of Systemic Lupus Erythematosus in a Mus musculus Model

Objective. Systemic lupus erythematosus (SLE) is a common chronic autoimmune inflammatory disease. According to recent studies, signaling through Toll-like receptor (TLR) protein, which promotes the production of inflammatory cytokines, leads to the development of SLE. TLR-inhibitory peptide 1 (TIP1) has been newly identified for the treatment of autoimmune diseases. Methods. The effect of TIP1 was analyzed in an SLE mouse model (MRL/lpr). The mice in the control treatment group (n=5) were administered an intravenous injection of phosphate-buffered saline twice weekly, whereas the mice in the TIP1 treatment group (n=6) were administered an intravenous injection of TIP1 (1 nmol/g) twice weekly. MRL/mpj mice (n=5) were selected as normal controls. The mice were injected for 4 weeks between 14 and 18 weeks of age, followed by assays of their spleen, kidneys, lymph nodes, serum, and urine. Results. The antinuclear antibody and inflammatory cytokine (interferon-α) in the serum as well as levels of albumin in the urine of the mice in the TIP1 treatment group had decreased when compared to those of mice in the control treatment group. Kidney inflammation in mice in the TIP1 treatment group was alleviated. The mRNA expression levels of TLR7- or TLR9-related downstream signaling molecules also decreased in all organs of the mice in the TIP1 treatment group. Conclusion. Intravenous treatment with TIP1 reduces symptoms and markers of inflammation in MRL/lpr mice. Hence, TIP1 is a promising medication for the treatment of SLE. (J Rheum Dis 2021;28:133-142)