Beneficiary Effects of Colchicine on Inflammation and Fibrosis in A Mouse Model of Chronic Kidney Disease

Introduction: 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 IL1 activation. Methods: : CKD was induced by administering an adenine diet to 8-week-old C57BL/6J mice. Mice were treated with colchicine (Col) (30µg/kg) or saline injections for 3 weeks, generating 4 groups: C, C-Col, CKD and CKD-Col. Results: : Uremic animals had an increase in inflammation indices in blood (neutrophils), liver and kidneys (p-STAT3, IL-6, SOCS-3). Increased kidney tubulin polymerization and caspase 1 in CKD, as well as kidney Mid88 and IRAK4 (downstream of IL1) were inhibited in CKD-Col. Kidney macrophage infiltration (F4/80 and MAC-2), the percentage of fibrotic area and TGFb mRNA levels were lower in CKD-Col Vs CKD. Conclusions: : colchicine improves kidney macrophage infiltration and fibrosis in CKD through inhibition of tubulin polymerization and Caspase 1 activation. Given its reported safety profile for long term anti-inflammatory therapy without increasing infection tendency, it may serve as novel therapeutic approach in CKD.