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Experimental Myelofibrosis

1975; Elsevier BV; Volume: 4; Issue: 2 Linguagem: Inglês

10.1016/s0308-2261(21)00086-2

1558-1977

W. Hunstein,

Eosinophilic Disorders and Syndromes

experimental infarction and mechanical trauma. Local interruption of blood flow by destruction of blood vessels, ligation, and embolisation result in scarring of the marrow. These processes are not related to MF in man, because there are only a few isolated cases reported where MF is due to vascular disease (Wepler, 1948, 1950). Moreover, the experimental lesions are reversible. toxic necrosis. Similar considerations apply to the administration of such myelotoxic substances as saponin and lead acetate. These substances cause vascular injury, may cause direct destruction of cells and certainly cause initial haemolysis. Again, the resulting MF is reversible, despite frank new bone formation (sclerosis). ionising radiation. Local irradiation of bone marrow produces local scars; continuous irradiation with an incorporated radionuclide leads in some animal species to moderate MF. Frank MF with many characteristics seen in MF in man can be provoked in rats by lethal whole-body radiation, followed by transplantation of allogenic marrow cells. This model should be reproduced, if only to settle whether it is reversible or not. viruses. Virus-induced MF, though most promising has not been studied much. This is clearly not a reversible but a self-perpetuating process. foreign protein. The administration of foreign protein with repeated injection of antigens takes a course via local antigen-antibody reactions and disseminated intravascular thrombosis to myelonecrosis. It results in generalised scarring with bone formation and resorption. There can be extramedullary haemopoiesis with splenomegaly. These alterations can be influenced by therapy with corticosteroids but not by antiphlogistics or azathioprine. The process is also reversible in this set-up. It is not an appropriate model for MF in man, because it is unlikely to yield further results unless further modifications are introduced. Download : Download high-res image (135KB)Download : Download full-size imageFigure 9. Experimental models of myelofibrosis. Figure 9. Experimental models of myelofibrosis. All the models mentioned demonstrate different ways of producing MF in animals. The initial stage in nearly all models is myelonecrosis, which is covered by scar tissue (fibrosis, sometimes with and sometimes without myeloid metaplasia in the spleen and other organs). This phase is followed by that of reorganisation and regression so long as the noxious stimulus remains absent. The only models in which an autonomous process is involved seem to be those of whole-body irradiated rats with allotransplantation, and virus-induced MF in the mouse. Further research should concentrate on these models. An attempt should be made to influence the other models by changing the grade of immunity of the animals. Concerning the question of reciprocal influences between different models, it might be helpful to introduce into the clearly defined experiments a multifactorial component in the form of substances that act on bone, such as parathormone, vitamin D, and sodium fluoride. The interpretation is difficult because the bone marrow has a standard response to different kinds of insult. Injury induces necrosis; necrosis induces scar formation. Even now after several decades of experimental research into MF we are still unable to state whether the ‘autonomous’ factor in MF in man is the chronic administration of small quantities of toxic substances, or an idiopathic proliferation of stimulated reticulum cells. Animal experiments have still not provided absolute proof of the aetiological significance of exogenous factors.