New Therapy of Myelofibrosis with an Antifibrotic Substance and a Macrophage Stimulant

1993 
In an animal experiment liver cirrhosis was induced by thioacetamide (TAA) to assess the influence of drugs on fibrosis. We attached pathological importance to the macrophages, the liver possessing the greatest macrophage population as Kupffer cells in the sinusoids. We had observed an increased proliferation of Kupffer cells after splenectomy in the rabbit in former investigations. Liver cirrhosis induced by TAA developed earlier after splenectomy and more intensively, maybe as a result of hyperplasia of the Kupffer cells [2,3]. The TAA changes were diminished distinctly or inhibited by trypan blue. A Kupffer cell stimulation by trypan blue was evident on electron-microscopic examination (see Fig. 1). Trypan blue is not suitable for the treatment of human beings because of an oncogenic effect. We considered clofazimine, another dye which has an effect on macrophages. Clofazimine is an antiphlogistic substance used in the treatment of leprosy [12]. We examined, by simultaneous administration of clofazimine and TAA, whether changes of the function of Kupffer cells could be correlated with the course of liver damage [4,5,6,13].
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