Fig. 1
Montelukast reduces peripheral and central inflammation in a mouse model of IL-1β-induced preterm brain injury. Systemic and central inflammation was assessed based on expression level of pro-inflammatory cytokines, IL-1β, IL-6 and TNF, in the liver and brain, respectively, measured by qPCR. The IL-1β treatment group (IL1, n = 7) showed increased cytokine expression at 4 h in the liver and the brain, compared to the saline (SAL, n = 6) and montelukast alone (MO, n = 4) treatment groups (A, C). These increases consistently returned to control levels following montelukast treatment, both in the brain, and for IL-6 in the liver (IL + MO group, n = 6). The cytokine response was substantially reduced by 24 h following the induction of the injury (B, D), though montelukast treatment still showed some amelioration (SAL n = 6, MO n = 6, IL1 n = 9, IL + MO n = 8). Brain IL-6 expression was measured 4 h after induction of systemic inflammation, and concomitant treatment with montelukast at 1, 3, 10 and 30 mg/kg (E). The IL-1β-induced increase in IL-6 was significantly reduced by all doses of montelukast in a dose-dependent manner (p = 0.0003 for IL + MO 1 mg/kg, < 0.0001 for all other doses, 1-way ANOVA; n = 3/group). Mass spectrometry analysis (0.5, 1 and 8 h: n = 8; 4 and 24 h: n = 12) showed a peak montelukast concentration in the plasma and brain at 4 h post-administration (F), with the brain concentration proportional to plasma concentration (R2 = 0.52, p > 0.0001; G). Data presented as mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001. SAL: saline; IL1: IL-1β; IL + MO: IL-1β + montelukast; MO: montelukast; IL: interleukin; TNF: tumour necrosis factor