Interleukin-1-α as a Modulator of Cytotoxic Drug Activity Against Human Cancer Cells

Abstract

Interleukin-1 (IL-1) is a monokine normally released by monocytes/ macrophages upon antigenic or chemical stimulation [1–3]. IL-1 has been shown to be an activator of lymphocytes and a stimulator of hematopoietic progenitor cells. In addition to its stimulatory activities, IL-1 has been reported to be cytotoxic to human melanoma and selected tumor cells in vitro [4–5] but stimulatory to fibroblasts [6]. More recently, it was reported that human recombinant IL-1 and interferon-y have synergistic antiproliferative activity in several human solid tumor cell lines but not in a colon and a lung carcinoma line [7]. The combination of IL-1 and tumor necrosis factor (TNF) has also been reported to have synergistic cytotoxicity in human and murine tumor cells [8]. We are interested in the possible use of IL-1 as a modulator of chemotherapy drug specificity and efficacy. We report here a study demonstrating that although IL-1 alone was only mildly cytotoxic, it can effectively augment the cytotoxicity of mechlorethamine and doxorubicin. The mechanism of synergy seems to reside in the improved delivery of lesions to cellular DNA by these cytotoxic drugs when IL-1 interfered with the DNA repair process.