Eosinophilia induced by interleukin-2 cancer immunotherapy may be associated with enhanced production of total IgE

It is known that interleukin-2 (IL-2) cancer immunotherapy may cause a noticeable increase in eosinophil number (1, 2). This biological effect is supposedly due to IL-2-induced increased production of interleukin-5 (IL-5) (3), the most important growth factor for eosinophil generation (4). IL-2-induced eosinophilia is possibly not just a simple epiphenomenon, but seems to affect the antitumor efficacy ofIL-2 itself, because of the potential cytotoxic properties ofeosinophils (5). In fact, eosinophilia has been proven to be associated with clinical antitumor response during IL2 treatment (1,2). Moreover, it has been shown that eosinophils are potentially cytotoxic to normal cells (6). Despite the marked increase in the absolute number of eosinophils which occurs during IL-2 therapy, no eosinophil-induced tissue damage has been reported in the literature (1,2); in particular no clinical signs of disorders related to eosinophilic tissue infiltration have been observed by the various authors. It is therefore likely that different subsets of eosinophils exist, with different toxic properties for normal tissues. From a pathological point of view, it has been observed that the rise in eosinophils which occurs in various human diseases is often associated with an enhanced total IgE synthesis (7). The IgE-mediated release of inflammatory substances and eosinophilic infiltration would both be responsible for tissue damage (7). In an attempt to better define the mechanisms and the biological significance of the eosinophilia that occurs during IL-2 cancer immunotherapy, we evaluated the changes in eosinophil number and total IgE levels in a group of cancer patients treated with subcutaneous IL-2. The study included 10 male patients (median age 54 years, range 46-68) with histologically confirmed metastatic renal cell carcinoma. They received IL-2 alone subcutaneously at a daily dose of 6 million IV for 5 days/week for 6 consecutive weeks. No patient received steroids during the immunotherapy. Venous blood samples were collected before the start of IL-2 treatment and at I-weekly intervals. Total IgE serum levelswere measured with the RIA method using commercially available kits (Pharmacia, Uppsala-Sweden). Normal values obtained in our laboratory (95% confidence limits) were below 100 KV/L. The data were statistically analyzed with Student's t-test and coefficient of correlation. Individual and mean eosinophil values and IgE levels observed before and during immunotherapy are reported in Table I. Before the start of IL-2 administration, total IgE levelswere within the normal range in all patients. During immunotherapy, the IgE levels became abnormally high in 3/10 (30%) patients, while a clear increase in eosinophil number was observed in all patients. The mean values of both eosinophils and IgE were significantly higher during immunotherapy than before treatment (eosinophils: p < 0.00I; total IgE: p < 0.05). No significant correlation was seen between eosinophil and IgE increases (r = 0.3). No allergic complications occurred in patients whose IgE levels increased markedly in response to IL-2 administration. The results of this preliminary study suggest that the eosinophilia which occurs during IL-2 immunotherapy may be associated with an enhanced production of total IgE in some cases, without, however, any apparent relation, since no correlation was observed between eosinophil and IgE increases. The biological