Histamine as an adjunct to immunotherapy

Abstract

Interleukin-2 and interferon-alpha have been used as therapeutic options in the treatment of certain malignancies such as metastatic malignant melanoma, acute myelogenous leukemia, and renal cell carcinoma. However, the outcome with these agents has been less than optimal. While experiments in vitro would lead one to believe that these agents would be useful therapeutic alternatives, the situation in vivo is confounded by the fact that the microenvironments of the tumor and surrounding tissue are infiltrated with monocytes and macrophages, which suppress the cytotoxic activity of T cells and natural killer cells. The mechanism by which this occurs is through the generation of reactive oxygen species that are responsible for apoptosis by both T cells and natural killer cells. Histamine abrogates this suppression, thus restoring the cytotoxicity of these cells. Therefore, the addition of histamine to regimens containing cytokines is expected to optimize cytokine therapy. Clinical trials with these regimens are under way in the treatment of metastatic malignant melanoma, acute myelogenous leukemia, and renal cell carcinoma. Results published thus far indicate that the addition of histamine to cytokine therapy is both safe and efficacious in the treatment of these diseases.