DEFECTIVE IN-VITRO GRANULOPOIESIS IN PATIENTS WITH ANOREXIA-NERVOSA

Patients with anorexia nervosa (AN) frequently suffer from a mild degr ee of anemia and from moderate leukopenia on top of their undernourish ed state and metabolic disarrangements. To evaluate in vitro granulopo iesis and its relationship to cytokine production and undernutrition, we have studied 10 adolescent girls with moderate AN (age range, 13.5- 18.0). Study methods included assessment of peripheral blood (PB) gran ulocyte-macrophage colony-forming cells (GM-CFC) of the patients and a ge-matched controls, and determination of plasma and conditioned mediu m (CM) of mononuclear cells levels of IL-1, IL-3, IL-6, granulocyte-ma crophage colony-stimulating factor (GMCSF) and tumor necrosis factor ( TNF), all of which may play a role in GM-CFC growth regulation. GM-CFC numbers were significantly lower in AN patients compared with the nor mal controls (13.09 +/- 11.15 vel-sus 39.33 +/- 26.61 colonies/5 x 10( 5) cells, p < 0.01). No inhibitory effect was found in either plasma o r CIM of patients with AN. However, when CM were applied to non-recomb inant human GM-CSF-stimulated normal bone marrow GM-CFC targets, the n umber of colonies stimulated by the CM of patients with AN was signifi cantly lower than those stimulated by the CM of the controls (73.5 +/- 20.1 versus 113.0 +/- 11.6, p < 0.025). GM-CSF concentrations in CM w ere significantly lower in patients with AN compared with normal contr ols, but no such differences were found in IL-I, IL-3, IL-6, or TNF co ncentrations. These results indicate defective in vitro granulopoiesis in AN patients, manifested by a reduction of both GM-CFC and GM-CSF. It has to be determined whether these changes are the result of the ba sic disease process or are they due to malnutrition.