EFFECTS OF DOXORUBICIN ON CARDIAC DENDRITIC CELLS IN HYPERTENSIVE RATS

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Histologic and immunohistochemical studies using specific monoclonal antibodies were made to evaluate the severity of the chronic cardiomyopathy and the quantitative changes in interstitial dendritic cells (antigen-presenting cells), T-helper lymphocytes, T- cytotoxic/suppressor lymphocytes and macrophages in the hearts of spontaneously hypertensive rats (SHR) treated with doxorubicin. In addition, an assessment was made of the modifications of the responses of these cell populations by pretreatment of the SHR with ICRF-187, which protects against doxorubicin cardiotoxicity. The results obtained by cell counts showed that doxorubicin treatment induces a marked increase in the numbers of interstitial dendritic cells, T-helper lymphocytes and macrophages in the heart, that such increases are dose-dependent, and that they are attenuated in a dose-dependent fashion by pretreatment with ICRF-187. Thus, this work shows that doxorubicin increases, rather than decreases, certain immune responses of the heart. These responses appear to be initiated by the interstitial dendritic cells (which serve as antigen-presenting cells) and are considered to be of importance in the pathogenesis of the cardiotoxicity induced by doxorubicin.