Immunomodulating effects of inhaled alkylating drug melphalan in asthmatic patients

Abstract

Melphalan (Alkeran) is an alkylating drug belonging to the nitrogen mustard family. It is known as cytostatic and immunosuppressive agent. Cytostatic effect of melphalan can be realized in the dose range of 0.6 to 1.4 mg/kg bodyweight or in the concentration of 0.1 mg/ml in vitro. At the same time the 100-fold lower concentrations of the alkylating agents still demonstrate their properties resulted from a selective block of cytokine receptors. Forty two patients with exacerbation of steroid-resistant asthma were enrolled into the trial. Twenty one subjects were treated with basic therapy only (the control group) and 21 others received the basic therapy and melphalan inhalations (0.1 mg daily). Inflammatory markers of the bronchoalveolar lavage fluid and blood were investigated. The combined therapy with melphalan provided a significant benefit compared with the basic therapy alone. Marked elevation in the bronchoalveolar lavage fluid cytokine level was observed in the patients treated with melphalan. This could be associated with the airway epithelium regeneration. A significant decrease in CD95 expression by the blood lymphocytes as well as a diminution of the lymphocyte resistance to glucocorticoids was also demonstrated.