EVIDENCE FOR EOSINOPHIL ACTIVATION IN CANCER-PATIENTS RECEIVING RECOMBINANT INTERLEUKIN-4 - EFFECTS OF INTERLEUKIN-4 ALONE AND FOLLOWING INTERLEUKIN-2 ADMINISTRATION

Interleukin-4 (IL-4) is a T-cell-derived cytokine that may mediate mur ine tumor rejection through the activation of host eosinophils. In ass ociation with a Phase I clinical trial of IL-4 in cancer patients, we have examined changes in eosinophil counts and characterized systemic eosinophil degranulation, As previously reported, IL-4 administration induced a modest eosinophilia in all 17 evaluated patients, Here, we r eport that IL-4 therapy induced systemic eosinophil degranulation base d on increases in serum major basic protein (MBP) (P = 0.018) and urin e MBP (P = 0.031), The increase in serum MBP was IL-4 dose dependent ( P = 0.001), Following the highest dose (600 mu g/m(2)/day) of IL-4 adm inistered, mean serum MBP levels were >2000 ng/ml, Skin biopsies of ra shes from patients receiving IL-4 revealed MBP deposition, Sera from e ight patients receiving IL-4 at 360 and 600 mu g/m(2)/day exhibited eo sinophil survival-enhancing activity (on days 3, 5, 7, and 9) signific antly above pretreatment (on day 1) activity (P values 0.0469, 0.0039, 0.0395, and 0.0313, respectively), This enhanced eosinophil survival could be neutralized by antibodies to IL-5, granulocyte-macrophage-col ony-stimulating factor, and IL-3, The eosinophil activation demonstrat ed in this trial may be relevant to the clinical effects of IL-4 in ca ncer patients, Furthermore, an association between IL-4 and eosinophil activation should be explored in other disease states.