Beneficiary Effects of Colchicine on Inflammation and Fibrosis in a Mouse Model of Kidney Injury

Low-grade inflammation is seen in many chronic illnesses, including chronic kidney disease (CKD). We have recently reported on beneficiary effects of anti-inflammatory treatment in the interleukin (IL-) 1 pathway on anemia as well as CKD extent in a mouse model. Colchicine has been shown to have beneficiary effects in several inflammatory conditions through various mechanisms, including inhibition of tubulin polymerization as well as caspase-1-mediated IL-1 activation.Kidney injury (KI) was induced by administering an adenine diet to 8-week-old C57BL/6J mice treated with colchicine (Col) (30 µg/kg) or saline injections for 3 weeks, generating 4 groups: C, Ccol, KI, and KIcol.KI animals had an increase in inflammation indices in the blood (neutrophils), liver, and kidneys (uromodulin, IL-6, pSTAT3). Increased kidney tubulin polymerization and caspase-1 in KI, as well as kidney Mid88 and IRAK4 (downstream of IL-1), were inhibited in KIcol. Kidney macrophage and polymorphonuclear infiltration (positive for F4/80 and MPO, respectively), the percentage of fibrotic area, and TGFβ mRNA levels were lower in KIcol versus KI.Colchicine inhibited tubulin polymerization and caspase-1 activation and attenuated kidney inflammation and fibrosis in a mouse model of adenine-induced KI. Given its reported safety profile for long-term anti-inflammatory therapy without increasing infection tendency, it may serve as novel therapeutic approach in CKD.