MODULATION OF CYTOKINES BY THE ALKYLLYSOP HOSPHOLIPID IIMOFOSINE

Ilmofosine, an alkyllysophospholipid, acts as an antiproliferative cyt ostatic drug. The mode of actions of the alkyllysophospholipids can be assigned to three principal effects: 1. Direct and selective cytoxici ty through interference with the metabolism of membranes. 2. Activatio n of macrophages. 3. Induction of terminal differentiation of tumor ce lls. An impact on the metabolism of membranes results also in changes within the cytokine network, regulating its balance by membrane bound receptors with affinity to effector molecules of the immune system. Th e influence on these molecules has been evaluated in vitro by measurin g the modulation of IL1 alpha, IL1 beta, IL2, TNF alpha, and IFN-gamma concentrations, representing key cytokines within the cytokine networ k. The investigations assessed whole blood samples of 12 healthy refer ences and 12 tumor patients. Furthermore stimulation assays were done with an optimal stimulatory compound for every single cytokine, respec tively. The results were as follows: IFN-gamma showed a general dose d ependent inhibition by Ilmofosine, IL2 dose dependent inhibition in re ferences and patients, TNF-alpha enhancement at low ilmofosine concent rations especially in patients with consecutive inhibition at higher d oses, IL1 alpha and IL1 beta similar course with initial increase at l ow doses with consecutive inhibition both in patients and references. The modulatory effect of ilmofosine on the cytokines investigated as i mportant mediators within the immune system demonstrates a major aspec t of the therapeutic potential of this interesting compound.