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Biomedical subjects

F Rovelli

Publications and source records attributed to F Rovelli.

191 records · Page 11Linked to original sources
PubMedDate not supplied

Relation between macrophage and T helper-2 lymphocyte functions in human neoplasms: neopterin, interleukin-10 and interleukin-6 blood levels in early or advanced solid tumors.

At present, it is known that there are two main mechanisms responsible for cancer-related immunosuppression, mediated by macrophages and by TH2 lymphocytes. The relation existing between macrophage- and TH2-mediated immunosuppression still remains to be understood. The present study was performed in an attempt to establish which is the correlation existing in cancer patients between IL-10 and neopterin levels, which reflect TH2- and macrophage-mediated suppressive events, respectively. The study included 40 solid tumor patients and 60 healthy subjects as controls. Serum concentrations of neopterin and IL-10 were measured by the RIA method and by an immuno-enzymetric assay, respectively. Because of its possible production both by TH2 and macrophages, serum levels of IL-6 were also determined. Neopterin, IL-10 IL-6 mean concentrations were significantly higher in cancer patients than in controls. Mean values of both neopterin and IL-6 were significantly higher in metastatic patients than in those with locally limited disease. IL-10 mean levels were also significantly higher in patients with metastatic disease. IL-6 levels were significantly correlated with those of neopterin, whereas no correlation was found between neopterin and IL-10 values. This preliminary study would suggest that macrophage- and TH2-mediated immunosuppression may occur independently in solid tumors, and that it becomes more evident with disease progression.

Adult↗
PubMedDate not supplied

Neuroimmunotherapy with low-dose subcutaneous interleukin-2 plus melatonin in AIDS patients with CD4 cell number below 200/mm3: a biological phase-II study.

A phase-II pilot clinical study was performed to evaluate the effects of low-dose subcutaneous IL-2 with the pineal hormone melatonin (MLT) in AIDS patients with CD4 counts below 200/mm3. The study included 11 patients. IL-2 was given subcutaneously at 3 million IU/ day in the evening for 6 days/week for 3 weeks. MLT was given orally at 40 mg/day in the evening every day, starting 7 days prior to IL-2. The treatment was substantially well tolerated, and in particular no cardiovascular or pulmonary complication occurred. An increase in CD4 cell number greater than 30% occurred in 4/11 (36%) patients, and CD4 cell mean values observed during the study were significantly higher with respect to those found before. In addition, the treatment induced a significant increase in mean number of lymphocytes, eosinophils, T lymphocytes, NK cells, CD25- and DR-positive lymphocytes. Finally, CD4/CD8 mean ratio significantly increased during the study. This preliminary clinical study suggests that the combined neuroimmunotherapy with low-dose subcutaneous IL-2 and MLT may improve the immune status also in AIDS patients with CD4 cell counts below 200/mm3, who generally do not respond to IL-2 alone.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Immunomodulatory properties of a pineal indole hormone other than melatonin, the 5-methoxytryptophol.

Several experiments have suggested that the pineal gland has an antitumor immunomodulatory action. Melatonin (MLT), the best known pineal hormone, has been shown to stimulate anticancer immune defenses during the night, corresponding to the period of its maximum blood levels, whereas it has no effect during the light phase of the day. At present, no study has been performed to investigate possible immunomodulating properties of other pineal indoles, such as 5-methoxytryptophol (5-MTL), whose circadian secretion would be opposite with respect to that of MLT, since it reaches its highest levels during the light phase of the day. In an attempt to analyze possible effects of 5-MTL on anticancer immunity, we have evaluated the action of 5-MTL (1 mg/ day orally at noon for 5 days) in 10 healthy volunteers on the two fundamental suppressive and immunostimulatory cytokines, consisting of IL-6 and IL-2, respectively. Serum levels of IL-2 and IL-6 were measured by an immunoradiometric method. Mean serum concentrations of IL-2 significantly increased on 5-MTL therapy, whereas those of IL-6 significantly decreased in response to 5-MTL. This preliminary study would suggest that the less known pineal indole 5-MTL, as well as MLT, has important immunomodulatory effects on cytokine secretions, including those involved in the antitumor immune response, by further confirming the essential role of the pineal as a central regulation of biological response modifier system. Several pineal alterations have been described in advanced cancer patients. According to the results of this study, the simultaneous administration of MLT during the dark phase and of 5-MTL during the light period of the day could further contribute to correcting pineal functions and to pilot the host anticancer immune reaction in an antitumor direction with respect to MLT alone.

Adjuvants, Immunologic↗
PubMedDate not supplied

Interleukin-2, melatonin and interleukin-12 as a possible neuroimmune combination in the biotherapy of cancer.

Suppressive events induced by macrophages and TH2 lymphocytes would represent the most important factors responsible for the in vivo reduced efficacy of IL-2 cancer immunotherapy. Previous studies have shown that IL-3 or the pineal hormone MLT may abrogate macrophage-related suppressive events during IL-2 immunotherapy, while TH2-mediated immunosuppression is not neutralized by MLT or IL-3. On the basis of previous experimental data suggesting the inhibitory effect of IL-12 on TH2 activation, this preliminary study has been performed in an attempt to evaluate the influence of IL-12 on TH2 stimulation induced by IL-2 alone or IL-2 plus MLT, by evaluating the release of IL-10, which represents the main suppressive factor produced by TH2 lymphocytes. Pure lymphocyte cultures were incubated for 4 days with IL-2 (100 Cetus U/ml), MLT (100 pg/ml), IL-12 (1 ng/ml), IL-2 plus MLT, IL-2 plus IL-12 or IL-2 plus MLT and IL-12. Mean medium concentrations of IL-10 were measured by Elisa. IL-2 alone significantly stimulated IL-10 secretion with respect to the control medium alone, while no difference was observed with MLT alone or IL-12. IL-2-induced stimulation of IL-10 secretion was not abrogated by a concomitant MLT incubation. On the contrary, IL-12 significantly diminished IL-10 release in response to IL-2, and this inhibitory effect was more pronounced when IL-2 was added in association with both IL-12 and MLT. This preliminary study would suggest that the two most important immunosuppressive events occurring during IL-2 therapy, which are mediated by macrophages and TH2-lymphocytes, may be abrogated by a concomitant administration of MLT and IL-12, respectively. Therefore, the association of IL-12 could further amplify IL-2 efficacy with respect to IL-2 alone or IL-2 plus MLT.

Humans↗
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

Anticancer neuroimmunomodulation by pineal hormones other than melatonin: preliminary phase II study of the pineal indole 5-methoxytryptophol in association with low-dose IL-2 and melatonin.

Despite several years of experimental observations, the clinical application of the neuroimmunomodulation is still at the beginning. The pineal gland plays a main role in mediating the link between psychoneuroendocrine and immune systems. Melatonin (MLT), which is the main pineal hormone produced during the night, has appeared to amplify IL-2 anticancer activity. Other pineal hormones, however, would have immunomodulatory activity, in particular 5-methoxytryptophol (5-MTT), which is mainly produced during the light phase of the day. Previous clinical studies have shown that low-dose IL-2 plus MLT may have therapeutic efficacy in advanced cancer patients with neoplasms generally resistant to IL-2 alone, with a tumor regression rate generally less than 20% and an acceptable toxicity. The present study was carried out to evaluate the efficacy of low-dose IL-2 in association with both MLT and 5-MTT. The study included 14 untreatable advanced solid tumor patients (lung cancer: 4; gastric cancer: 3; mesothelioma: 2; hepatocarcinoma: 2; pancreatic cancer: 1; melanoma: 1; colon cancer: 1). IL-2 was injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, by repeating a second cycle after a 21- day rest period. Both MLT and 5-MTT were given orally at 40 mg/day in the evening and at 1 mg/day at noon. The clinical results, as evaluated by WHO criteria after each cycle, consisted of partial response (PR) in 4/14 (29%) (lung cancer: 2; hepatocarcinoma: 1; mesothelioma: 1), stable disease (SD) in 6 and progressive disease in the last 4 patients. The treatment was extremely well tolerated in all patients, and in particular no fever greater than 38 degrees C occurred. These preliminary results show that the neuroimmunotherapy with low-dose IL-2 plus two pineal hormones, MLT and 5-MTT, is a well tolerated and potentially effective cancer therapy of untreatable advanced solid tumor patients, with results apparently superior with respect to those previously described with IL-2 plus MLT alone.

Adjuvants, Immunologic↗
PubMedDate not supplied

Acute endocrine effects of interleukin-12 in cancer patients.

IL-12, which play a fundamental antitumor role, would be also involved in the physiological regulation of neuroendocrine and immune interactions. At present, however, there are no data about the endocrine effects of IL-12. This preliminary study was performed to investigate the acute endocrine effects of IL-12 in metastatic renal cell cancer patients. Each IL-12 injection consisted of 0.5 micrograms/kg/bw subcutaneously in the morning. The study has evaluated the effects of 6 different injection cycles. Serum samples were collected before, and 4, 8 and 12 hours from IL-12 injection. In each sample, we have measured by the RIA method serum levels of GH, PRL, TSH, FSH, LH, T3, T4, cortisol, testoterone, estradiol and the pineal hormone melatonin. No significant change occurred in TSH, FSH, LH, T3, T4, testoterone and melatonin mean serum levels in response to IL-12 administration. In contrast, cortisol, PRL and estradiol significantly increased after Il-12 injection. GH also increased in response to IL-12, without however, significant differences with respect to the baseline values. This preliminary study shows that the acute subcutaneous injection of IL-12 may influence the endocrine secretions in humans. In particular, IL-12 would stimulate the secretions of cortisol, PRL and estradiol. Therefore, this study would further confirm that IL-12 may act as biological response modifier in humans, not only on the immune system, but also on the neuroendocrine functions.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Melatonin as a new possible anti-inflammatory agent.

Several experiments have suggested that the pineal hormone melatonin (MLT) may regulate cancer growth by exerting both oncostatic and immunomodulating effects. In particular, MLT would stimulate the anticancer immunity induced by interleukin-2 (IL-2). Recent studies seem to suggest that the activation of the inflammatory response may counteract the anticancer efficacy of IL-2 immunotherapy because of the immunosuppressive action of inflammatory-related cytokines, mainly IL-6. At present, it is still unknown whether MLT may influence host immune antitumor defences by modulating the inflammatory response. To analyze this hypothesis, we have evaluated the effects of a chronic administration of MLT on some of the commonly used markers of inflammation, including erythrosedimentation rate (ESR), IL-6, neopterin and SIL-2R, in patients with evidence of activation of the inflammatory response due to advanced solid neoplasms or auto-immune diseases. The study included 14 patients (solid tumors: 9; autoimmune diseases: 5). MLT was given orally at 20 mg/day during the dark phase of the day for 7 consecutive days. Mean serum levels of IL-6, neopterin and SIL-2R significantly decreased in both groups of patients. ESR values also decreased on therapy, without, however, significant differences. This preliminary study shows that the pineal hormone MLT may inhibit the acute inflammatory reaction. Therefore, because of the immunosuppressive section of inflammation-related cytokines, this study could suggest that MLT may contribute to the generation of the immune reaction against cancer at least in part by removing the immunosuppression related to the activation of the inflammatory response.

Adjuvants, Immunologic↗
PubMedDate not supplied

Correlation between IL-12 and IL-2 blood levels in the metastatic neoplastic disease: a possible inhibitory feedback system regulating their secretion.

Despite the great importance of IL-2 and IL-12 in activating the anticancer immune response in humans, cancer-related physiopathology of their secretion needs to be better investigated. IL-2 blood levels have been proven to decrease in the advanced neoplastic disease, whereas preliminary data would suggest an enhanced secretion of IL-12 in metastatic cancer patients. This study was performed to analyze IL-2 levels in relation to those of IL-12 in metastatic solid neoplasms. The study included 40 untreated metastatic cancer patients. Serum levels of both IL-2 and IL-12 were measured by ELISA. Abnormally low blood levels of IL-2 and elevated values of IL-12 were observed in 16/40 and in 18/40 patients, respectively. Moreover, patients with IL-2 deficiency showed significantly higher mean levels of IL-12 than patients with normal values of IL-2. This preliminary result, by showing an increased secretion of IL-12 in advanced cancer patients with IL-2 endogenous deficiency, would suggest the existance of a possible feedback mechanism operating between macrophage release of IL-12 and T lymphocyte secretion of IL-2.

Adult↗
PubMedDate not supplied

Physiopathology of IL-12 in human solid neoplasms: blood levels of IL-12 in early or advanced cancer patients, and their variations with surgery and immunotherapy.

Experimental studies have shown that IL-12 plays an important role in the activation of the anticancer immune defenses. Unfortunately, at present the behavior of IL-12 secretion in human neoplasms remain to be established. In an attempt to draw some preliminary data about IL-12 secretion in human cancer, in the present study we have evaluated serum levels of IL-12 in a group of non-metastatic and metastatic solid tumor patients in relation to the survival time, and their changes in surgically treated cancer patients and in metastatic patients undergoing immunotherapy with IL-2. Mean serum levels of IL-12 were significantly higher metastatic patients (n = 40) than in those with locally limited solid neoplasm (n = 16). Moreover, within the metastatic group, the percent of 1-year survival was significantly higher in patients with abnormally elevated blood concentrations of IL-12 than in those with normal values. In the group of 10 patients surgically treated for gastrointestinal tract tumors, the surgical operation induced a significant decline in IL-12 mean serum levels. Finally, in a group of 23 metastatic renal cell cancer patients treated with IL-12 immunotherapy (6 million IU/day S.C. for 6 days/week for 4 weeks), the treatment was associated with a significant and progressive increase in IL-12 mean values. Moreover, serum mean levels of IL-12 observed in therapy in patients with response or stable disease were significantly higher than those found in progressing patients. This preliminary study seems to suggest that the evidence of high levels of IL-12 may have a favourable prognostic significance in solid tumor patients, either in baseline conditions or in response to IL-2 cancer immunotherapy.

Adult↗