Colchicum plant11/19/2023 ![]() ![]() In addition to the use of colchicine in acute flares, evidence supports its use as a prophylactic agent in certain patients with chronic gout. Importantly, they also noted that the high-dose was associated with more diarrhea and vomiting. The authors found a comparable response rate in the low-dose group versus the high-dose group with both found to be superior to placebo. In this study, 184 patients experiencing acute gout flares were randomized to either a low dose regimen (1.2 mg dose followed by one 0.6 mg dose one hour later), a high-dose regimen (1.2 mg dose followed by one 0.6 mg dose every hour up to a maximum of 4.8 mg), or placebo. The AGREE (Acute Gout Flare Receiving Colchicine Evaluation) trial was the first randomized, placebo-controlled trial to compare low and high-dose colchicine. The authors found that two-thirds of colchicine-treated patients experienced pain reduction within 48 hours, compared with one-third of patients in the placebo group experiencing similar response however, patients reported diarrhea prior to relief of symptoms. In the first randomized, placebo-controlled trial assessing the efficacy and toxicity of colchicine in acute gout, patients were treated with an initial 1 mg dose followed by sequential doses of 0.5 mg every 2 hours until either significant symptomatic relief or intolerance. 2 Despite its longstanding use, few randomized controlled trials have evaluated its efficacy empirically. As noted above, all of these pathways are affected by colchicine. ![]() Inflammation in gout is mediated by a combination of neutrophil and macrophage activation, leukocyte adhesion molecules, inflammasome activation as well as IL-1β production. 8 Given these extensive effects on inflammation, it is not surprising that the use of colchicine has been explored in a number of inflammatory conditions.Ĭolchicine has been known as a treatment for gout for several millenia. 4 In keeping with this effect on inflammatory modulators, in vivo and in vitro studies demonstrate decreased levels of the proinflammatory cytokines IL-1β, IFNγ, IL-18 and IL-6 with colchicine use. 7īy impairing vesicular trafficking, colchicine is able to both decrease TNF-α receptor expression on macrophages (preventing activation) and interrupt granule release in mast cells (preventing degranulation). 6 Neutrophil function is additionally compromised by colchicine via suppression of neutrophil superoxide production, a key contributor to the inflammatory response seen in neutrophil activation. 5 It further prevents neutrophil migration by decreasing the inducing effects of platelet activating factor and leukotriene-β4 on neutrophil adherence. The drug decreases neutrophil L-selectin expression and modulates E-selectin expression on the cell surface of endothelial cells, thereby impairing neutrophil recruitment. Microtubules (red) were imaged by immunostaining with monoclonal anti-alpha tubulin antibody and the DNA in the nucleus (blue) was revealed by Hoechst stain.Ĭolchicine impairs neutrophil function by impacting inflammatory pathways and mediators of neutrophil activation. The cells are UW-BCC1 cells (58), grown on glass coverslips and imaged. The exact mechanism by which this colchicine induced MT destabilization leads to alteration of cell function remains unclear.įluorescence microscopy images of basal cell carcinoma cell line showing the microtubule cytoskeleton and the nucleus. Colchicine binds to tubulin heterodimers and alters the tubulin conformation, allowing the tubulin dimer-colchicine complex to add to the growing end of a MT but preventing any further growth, thus poisoning the dynamics of that MT. Structurally, MT are hollow cylinders composed of protofilaments, which in turn are made from αβ-tubulin heterodimers polymerized end to end. These dynamics allow changes in MT distribution and in overall cell shape ( Figure 3). ![]() 3, 4 MT dynamics originate in a balance of polymer growth and shrinkage, mostly at the MT end that is distal to the nucleus. MTs serve as a major part of our cellular cytoskeleton, and are essential to cellular functions such as mitosis, as well as intracellular organelle and vesicle trafficking. In the 1950’s and 1960’s the microtubule (MT) was identified as the primary cellular target. Despite its use for thousands of years, colchicine’s exact mechanism of action is still being explored. ![]()
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