A Crucial Role for Interleukin-18/IL-18R Signalling Axis in the Development of Renal Inflammation and Elevated Blood Pressure in 1 Kidney/DOCA/Salt-Induced Hypertension

Interleukin-18 (IL-18) is a pro-inflammatory cytokine released downstream of inflammasome activation that is elevated in hypertensive patients. However, whether IL-18 plays a causal role in hypertension is unknown. The aims of the current study are to characterise renal expression of IL-18 and its receptor (IL-18R) in hypertensive mice, and to determine the effect of IL-18 and IL-18R deficiency on the development of hypertension and renal inflammation. Hypertension was induced in male wild-type (WT), RAG1−/− and IL-18−/− mice by uninephrectomy and treatment with deoxycorticosterone acetate (2.4 mg/d, s.c.) and saline (0.9%) drinking water (1K/DOCA/salt). Control mice received uninephrectomy, a placebo pellet and normal drinking water (1K/placebo). RAG1−/− mice received either PBS, WT or IL-18R−/− T cells via tail vein three weeks before 1K/DOCA/salt treatment. Blood pressure (BP) was measured via tail cuff. After 21 days, kidneys were harvested to assess: hypertrophy; mRNA expression of IL-18, IL-18R (qRT...