MEDROXYPROGESTERONE ACETATE REDUCES THE IN-VITRO PRODUCTION OF CYTOKINES AND SEROTONIN INVOLVED IN ANOREXIA CACHEXIA AND EMESIS BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF CANCER-PATIENTS/

Medroxyprogesterone acetate (MPA) is widely used in oncology both in t he treatment of hormone-related cancers and as supportive therapy in a norexia/cachexia syndrome (ACS), but conclusive data are not yet avail able to explain its anticachectic effect. ACS is characterised by weig ht loss, changes in metabolism, reduction of appetite, nausea and vomi ting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tum our necrosis factor alpha (TNF alpha), are involved in the pathogenesi s of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic ce lls including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 1 0 cancer patients in advanced stage of disease (6 head and neck, 2 col on, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, an ti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the prod uction of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL -2R) subunities (CD25 and CD122) were studied. The addition of MPA sig nificantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 mu g/ml was also capable of reducing th e levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the perc entage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb. (C) 1997 Elsevier Science Ltd.