Interleukin-12 in early or advanced cancer patients.

Interleukin-2 (IL-2) and interleukin-12 (IL-12) may represent the most important antitumour cytokines in human neoplasms. IL-2 blood levels decrease in advanced solid malignancies, but currently there are no data on IL-12 secretion in cancer patients. This study was performed to obtain preliminary data about IL-12 secretion in patients with solid malignant tumours, either in relation to the extension of disease, or to other cytokines, including IL-2, IL-6 and IL-10. The study included 40 solid cancer patients, 24 of whom showed distant organ metastases. Cytokine serum levels were measured by an enzyme immunoassay of blood samples collected during the morning. No patient had abnormally low levels of IL-12, but the levels were high in 14/14 (35%) patients. Mean levels of IL-12 were significantly higher in metastatic patients compared with non-metastatic patients (P < 0.05). Moreover, metastatic patients with high blood concentrations of IL-12 showed significantly lower levels of IL-10 than metastatic patients with normal IL-12 values, while no difference was seen in IL-2 mean concentrations. IL-6 mean levels were lower in metastatic patients with increased IL-12 levels, but this was non-significant. This preliminary study shows that advanced solid cancers are not characterised by a diminished secretion of IL-12, but rather IL-12 levels tend to be abnormally high in metastatic cancer patients.

Clinical significance of erythrosedimentation rate in cancer in relation to cytokine production: correlation with high IL-6 and low IL-2 blood concentrations.

Despite its well documented unfavourable prognostic significance in several human diseases, including cancer, the cytokinic mechanisms responsible for an increased erythrosedimentation rate (ESR) still remain to be better analyzed and defined. The recent possibility to measure cytokine concentrations in the blood of patients has allowed us to explore the possible relation between ESR values and endogenous cytokine secretions. This preliminary study was performed to evaluate the relationship between ESR values and serum levels of IL-2 and IL-6, which represent the most important cytokines responsible for the activation and the suppression, respectively, of host anticancer immune reaction. The study included 33 consecutive solid tumor patients, 22 of whom showed distant organ metastases. Abnormally high values of ESR were present in 21 patients, including 18/22 metastatic patients and 3/11 nonmetastatic patients. Patients with elevated values of ESR showed significantly higher mean levels of IL-6 and significantly lower mean concentrations of IL-2 with respect to those found in patients with normal ESR values. These results would show that cancer-related increase in ESR values is associated with low levels of IL-2 and high levels of IL-6. Since IL-2 plays an essential role in the anticancer immunity and IL-6 may suppress the antitumor immune defenses, the evidence of low levels of IL-2 and high values of IL-6 in cancer patients with increased ESR values would explain the unfavourable prognostic significance of high ESR values in human neoplasms.

Effects of granulocyte-macrophage colony stimulating factor on soluble interleukin-2 receptor serum levels and their relation to neopterin and tumor necrosis factor-alpha in cancer patients.

SIL-2R levels mainly depend on a T lymphocyte production. The mechanisms responsible for the elevated blood concentrations of SIL-2R in advanced solid tumors are still unknown. To investigate the role played by the monocyte-macrophage system on SIL-2R release, we have evaluated serum levels of SIL-2R in 10 head and neck cancer patients during GM-CSF subcutaneous administration (3 mcg/kg/day for 11 consecutive days). Serum levels of TNF and neopterin, both produced by macrophages, were also measured. SIL-2R mean concentration significantly enhanced in response to GM-CSF, and their rise positively correlated to that in TNF and neopterin values, while lymphocyte mean number did not increase during the study. The present results represent the first in vivo demonstration that SIL-2R release is related to macrophage activation, rather than to depend only on lymphocyte proliferation.

Inhibition of tumor necrosis factor-alpha secretion by pentoxifylline in advanced cancer patients with abnormally high blood levels of tumor necrosis factor-alpha.

TNF, in addition to its antitumor activity, would play an important role in the pathogenesis of cancer-related severe complications, including ARDS and DIC. Therefore, the modulation of TNF secretion could be important in the supportive care of advanced cancer patients. At present, PTX is the only drug which has been proven to be able to inhibit in vitro the release of TNF. The present study was performed to evaluate the effect of PTX on TNF blood concentrations in disseminated cancer patients with abnormally high TNF values. The study included 14 cancer patients, with initial or conclamate signs of ARDS (n = 8) or DIC (n = 6). PTX was given intravenously at a dose of 300 mg/day for 7 days. Mean serum levels of TNF significantly decreased in response to PTX therapy, and they returned to normal range in 5/14 patients. These preliminary data would suggest that PTX may be considered as a biological response modifier, capable of inhibiting TNF secretion in humans, with a following potential use in the treatment of cancer-related severe complications.

Tumor necrosis factor in solid tumors: increased blood levels in the metastatic disease.

TNF, a cytokine produced by macrophages, is able either to exert an antitumor activity, or to determine severe clinical complications, such as cachexia and septic shock. Increased blood levels of TNF have been described in cancer patients. The present study was performed to better define TNF secretion in patients with solid tumors. The study included 48 cancer patients (lung cancer: 22; colon cancer: 11; breast cancer: 10; renal cancer: 5), and among them 27 showed distant organ metastases. TNF serum levels were measured by IRMA method. The control group comprised 40 healthy subjects. TNF levels were also evaluated in relation to those of SIL-2R, whose increase seems to be associated with an unfavorable prognosis in cancer. High levels of TNF were seen in 27/48 (56%) patients. Mean levels of TNF were significantly higher in cancer patients than in controls. Moreover, within the cancer group, TNF mean values were significantly higher in metastatic patients than in those without metastases; the highest levels were observed in patients with visceral lesions as dominant metastasis sites. Finally, patients with high TNF concentrations showed significantly higher mean levels of SIL-2R than those with normal values. This study shows that the neoplastic metastatic disease is associated with an exaggerated TNF secretion.