Effects of granulocyte colony stimulating factor on the specific macrophage marker neopterin in cancer patients

Sirs, In contrast to granulocyte-macrophage colony stimulating factor (GM-CSF), which may determine an increase in both neutrophil and monocyte numbers, it has been demonstrated that granulocyte-colony stimulating factor (G-CSF) selectively stimulates neutrophil production (1). However, most clinical studies have addressed only the evaluation of neutrophil and monocyte numbers in response to G-CSF rather than the investigation of the functional activity ofcells (I). It has been shown that neopterin levels in blood reflect the activation ofthe macrophage-monocyte system (2), mainly macrophage-mediated suppression of lymphocyte activities, including interleukin production (3). In fact, macrophages would play a major role in mediating the suppression of interleukin-2-dependent anticancer immune response (4), and abnormally high blood concentrations ofneopterin have been described in patients with widely disseminated tumor and a poor prognosis (5). To evaluate the possible influence of G-CSF on macrophage functions we analyzed the changes in neopterin secretion in cancer patients during G-CSF therapy. This preliminary study included 14 patients with advanced solid tumors who underwent G-CSF therapy because of chemotherapy-induced neutropenia. The median age of the patients was 56 years (range 42-67). Tumor histology was: 8 breast cancers, 3 lung cancers, I head and neck cancer, I uterine cervix carcinoma, I testicular cancer. The following chemotherapy combinations were administered: FEC (5-fluorouracil, epirubicin, cyclophosphamide) for breast cancer; PE (cisplatin, etoposide) for lung cancer; PEB (cisplatin, etoposide, bleomycin) for testicular cancer; carboplatin plus 5-fluorouracil for cervix carcinoma and head and neck cancer. All patients showed leukopenia and neutropenia at the time of the study. Human recombinant G-CSF was injected subcutaneously at a daily dose of 0.3 mg every day for 7 consecutive days. Venous blood samples were collected the morning before treatment and at the end of G-CSF injection. Serum levels of neopterin were measured with the RIA method by means of commercially available kits (Henning, Berlin, Germany). The results were reported as mean ± SE and statisticaly analyzed by Student's t test, analysis ofvariance and coefficient ofcorrelation, as appropriate. Normalization of both leukocyte and neutrophil numbers, with values greater than 3,500 and 2,000 cells/rum", respectively, was achieved in 9/14 (65%) patients, while the remaining 5 patients still presented cell numbers below the normal range in response to G-CSF injection. Changes in the mean neopterin are reported in Table I. The mean neopterin levels were significantly higher at the end of G-CSF injection than before therapy (P < 0.05). Moreover, the mean neoptenn increase was significantly higher in on-responder patients than in those with G-CSF-induced normalization of leukocytes and neutrophils (4.2 ± 0.5 vs 1.1 ± 0.3 ng/ml, P < 0.01). Nevertheless, changes in neopterin secretion and neutrophil and leukocyte variations were not significantly correlated. This preliminary study suggests that G-CSF may