Mechanism of Action of Colchicine in Acute Urate Crystal-Induced Arthritis

Abstract

A B S T R A C T Phagocytosis of urate crystals by human or rabbit neutrophils induces the synthesis and release of a glycoprotein, the crystal-induced chemotactic factor (CCF), which is chemotactically active both in vitro and in vivo. It has been proposed that CCF is a prime mediator of the acute gouty attack. Colchicine has been shown to decrease the production and release of this factor in vitro. In these studies, colchicine, at nonleukopenic doses, is shown to abrogate the acute arthritis induced by monosodium urate crystals in rabbits, but to have no effect upon the arthritis induced by the injection of the purified cell-derived chemotactic factor. Serum colchicine levels were 0.48-0.58 ,uM at 30 min and 0.12-0.3 AM at 90 min after intravenous injection of 0.2 mg/kg colchicine. Peripheral blood polymorphonuclear leukocytes obtained from colchicine-treated animals migrated normally towards a chemotactic stimulus but failed to produce CCF after phagocytosis of monosodium urate crystals. The dialyzed synovial fluid from rabbits injected with microcrystalline sodium urate contained chemotactic activity that was not present when animals were also given intravenous colchicine or injected intra-articularly with the chemotactic factor formyl-methionyl-leucyl-phenylalanine.Furthermore, the synovial fluid from rabbits injected with microcrystalline sodium urate significantly decreased 1251-CCF binding to neutrophils. The binding of '25I-CCF to its neutrophil receptor was not significantly reduced by the synovial fluid of colchicinetreated rabbits nor by the synovial fluid ofcontrol rabbits injected with the chemotactic factor formyl-methionylleucyl-phenylalanine. Colchicine (10 and 0.1 AM) was shown to have no effect upon the binding of 125I_CCF to its cell receptor.

Intake of different hays with presence of Colchicum autumnale by rabbits

“…This could imply a preference of the rabbits for MeS, supposing that their stems and leaves were easier to grab. Spilberg et al (1979) reported the first adverse effects when animals were exposed to 0.2 mg/kg BW of colchicine, which is less than the exposure of 0.8 and 1.2 mg/kg BW in the maximal level group in our study. The question about whether the appearance of MeS refusals in the maximal dose group (on av.…”

“…However, impact of the colour on consumption was not tested in this study, because we chose to treat colour as a factor in the buying decisions of pet owners. Therefore, even if owners (commercial breeders as well as pet owners) were shown to buy hay of an intense green colour rather than a yellow hay (Stainmesse 2015), it should have no impact on the sale of the tested hays.…”

“…However, a higher fibre content and lignification, consequences of a late harvest, would reduce the nutritional value of such hay for ruminants (Korva and Tuori, 1986). The organoleptic properties of hay from grasslands with high environmental values represent a high-value hay appreciated by herbivorous pet owners (Stainmesse, 2015). Moreover, absence of hay in the diet could increase overweight as well as dental diseases, highlighting the need for hay in a rabbit's diet on health grounds (Lord, 2014;Prebble et al, 2015).…”

Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B.

“…In this respect, hFpB contrasts with C5a, fMLP, or LTB4 and resembles instead a factor generated from plasma by superoxide (48) and the synthetic tripeptide, gly-his-gly (49), which also causes PMN chemotaxis without causing PMN secretory responses.…”

Hiperuricemia y altura.

“…Isaías Spilberg a fines de los 70 e inicios de los 80, se dedicó a investigar el rol quimiotáctico que ejercen los cristales de urato monosódico sobre el leucocito y la interrupción del mismo con colchicina (3,4).…”