Does the lack of the P-glycoprotein efflux pump in neutrophils explain the efficacy of colchicine in familial Mediterranean fever and other inflammatory diseases?
Colchicine is an alkaloid drug commonly used in familial Mediterranean fever (FMF), gout, Behcet's syndrome, psoriasis and Sweet's syndrome. The exact mechanism of its action in these diseases is not entirely known. However, it has been shown that colchicine may inhibit neutrophil chemotaxis, thereby decreasing the inflammatory process. Recently, it was shown that colchicine accumulates in neutrophils in higher concentrations than in lymphomonocytes. Studies dealing with the multiple drug resistance (MDR) issue disclosed that neutrophils lack the P-glycoprotein (P-gly) membranal pump (encoded by the MDR1 gene). We propose that the preferential accumulation of colchicine in neutrophils compared with lymphomonocytes is due to the absence of the P-gly efflux pump in the former. This may explain the effectiveness of colchicine in diseases where increased chemotaxis is evident. The hypothesis may also provide an explanation for FMF patients who do not respond to the drug.
Ben-Chetrit
E
E
Department of Medicine, HadassAh University Hospital, Jerusalem, Israel.
Levy
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D002121:Calcium Channel Blockers; D002885:Chromosomes, Human, Pair 16; D002897:Chromosomes, Human, Pair 7; D003078:Colchicine / Q000627:therapeutic use*; D010505:Familial Mediterranean Fever / Q000188:drug therapy* / Q000235:genetics; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy*; D007962:Leukocytes / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D012235:Rhodamines / Q000493:pharmacokinetics; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D006074:Gout Suppressants; D012235:Rhodamines; D014700:Verapamil; D003078:Colchicine