Does the lack of the P-glycoprotein efflux pump in neutrophils explain the efficacy of colchicine in familial Mediterranean fever and other inflammatory diseases?
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Abstract
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.