Synergistic effects of locally administered cytostatic drugs and a surfactant on the development of delayed-type hypersensitivity to keyhole limpet haemocyanin in mice.

The immunomodulating effects of two locally administered cytostatic drugs, the active cyclophosphamide-derivative Z 7557 and the plant alkaloid VP-16, were compared with the effects of systemically administered cyclophosphamide and several established adjuvants: Freund's complete adjuvant, dextran sulphate, and dimethyl dioctadecyl ammonium bromide (DDA). All agents tested promoted the development of delayed-type hypersensitivity (DTH) to keyhole limpet haemocyanin (KLH) in mice. Locally administered cytostatic drugs were the most effective immunostimulatory compounds, whereas DDA was the least toxic agent tested. In order to increase the effectiveness and/ or reduce the toxicity of these agents we tested the efficacy of combinations of cytostatic drugs and DDA to enhance DTH. The results show that DDA and suboptimal amounts of locally administered cytostatic drugs act synergistically on DTH.