Eosinophils also participate in transplant rejection, Graft-versus-host disease, the destruction or walling off of foreign objects, and the killing of cancer cells. In conducting these functions, eosinophils enter tissues that they do not normally occupy.When overproduced and over-activated, such as in cases of eosinophilic myocarditis, eosinophils behave as though they were attacking a foreign or malignant tissue: they enter a seemingly normal organ such as the heart, misdirect their reactive oxygen species and armamentarium of preformed molecules toward seemingly normal tissue such as heart muscle, and thereby produce serious damage such as heart failure. Animal model studies suggest reasons why eosinophils are directed to and injure the heart muscle. Mice made hypereosinophilic by the forced overexpression of an interleukin-5 transgene (interleukin 5 stimulates eosinophil proliferation, activation, and migration) develop eosinophilic myocarditis. A similar eosinophilic endocarditis occurs in mice immunized with the cardiac muscle protein, mouse myosin. In the latter model, endocarditis is reduced by inhibiting the cytokine interleukin-4 or eosinophils and is exacerbated by concurrently blocking two cytokines, interferon gamma and interleukin-17A. Finally, certain eosinophil-attracting agents, viz., eotaxins, are elevated in the cardiac tissue of myosin-immunized mice that are concurrently depleted of interferon gamma and interleukin-17A. Eotaxins are also elevated in the cardiac muscle biopsy specimens of individuals with eosinphilic myocarditis compared to their levels in non-eosinophiliic myocarditis. These findings suggest that eosinophilic myocarditis is caused by the abnormal proliferation and activation of eosinophils and that their directional migration into the heart is evoked by a set of cytokines and chemoattractants in mice and possibly humans.
History
In 1936, the famed Swiss physician Wilhem Löffler first described heart damage that appeared due to massive cardiac eosinophil infiltrations and was associated with excessively high levels of blood eosinophils. Subsequent cases of this disorder, termed Loeffler endocarditis, were found to occur in about 20% of individuals diagnosed with the hypereosinophilic syndrome. Loefflers and the latter cases had pathological features of eosinophil infiltrations not only into the hearts myocardium but also its epicardium (i.e. lining of the heart chambers). Although eosinophilic myocarditis due to other underlying causes may show little or no eosinophil infiltrations into the endocardium, Loeffler endocarditis is considered an important form of the disorder. == References ==