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      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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      Medical Hypotheses
      Elsevier BV

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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.

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          Author and article information

          Journal
          Medical Hypotheses
          Medical Hypotheses
          Elsevier BV
          03069877
          November 1998
          November 1998
          : 51
          : 5
          : 377-380
          Article
          10.1016/S0306-9877(98)90031-7
          9848464
          84488d40-099c-4fcb-948a-ad555fb6d061
          © 1998

          https://www.elsevier.com/tdm/userlicense/1.0/

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