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.

Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure.

OBJECTIVES: The goal of this study was to assess long-term neurobehavioral effects associated with low airborne concentrations of manganese in a ferroalloy plant. METHODS: During a period of forced cessation of work (1 to 42 d) neurobehavioral performance on tests of simple reaction time, finger tapping, digit span, additions, symbol digit, and shapes comparison was evaluated for 58 workers exposed from 1 to 28 (mean 13, SD 7) years to manganese. Airborne manganese concentrations in total dust had been reduced in the last 10 years from 70-159 micrograms x m-3 (geometric means in different areas) to 27-270 micrograms x m-3. For each worker, manganese concentrations in blood and urine were measured, and a cumulative exposure index was also calculated. RESULTS: Blood manganese and urinary manganese ranged from 4 to 18 micrograms x 1-1 (0.07 to 0.03 mumol x 1-1) and from 0.7 to 7 micrograms x 1-1 (0.01 to 0.13 mumol x 1-1) respectively. Significant relationships were found between the blood manganese and urinary manganese levels and between these biological measures and the cumulative exposure index. Correlations were also found between the blood manganese level, the urinary manganese level, and the cumulative exposure index and the following tests: finger tapping, symbol digit, digit span, and additions. The correlation coefficients increased as the latency time after the cessation of exposure and work seniority increased. CONCLUSIONS: The results support the hypothesis that the neurobehavioral effects observed at exposure levels well below current occupational standards are related to manganese body burden, which is better reflected by the blood manganese level after the cessation of exposure.

Neuroendocrine response to psychological performance testing.

Neuroendocrine changes associated with performance testing requiring sustained attention were assessed in eight normal male subjects. To verify whether the hormonal pattern was modified by chronic stimulation of opiate receptors, eight heroin addicts also were studied. Reaction times were similar in normal and addict subjects. In normal individuals, consistent and significant increases in plasma ACTH and beta-endorphin and in urinary epinephrine and norepinephrine were observed, whereas serum prolactin (PRL) progressively decreased over the testing period. Despite maintained performance capabilities, heroin addicts showed a blunted response of ACTH and a paradoxical decrease in endorphin levels. As the normal subjects, both epinephrine and norepinephrine in urine showed the same significant increase over baseline values. Serum PRL showed a similar trend towards decreased values over the testing period in both groups.

Long-lasting impairment of neuroendocrine response to psychological stress in heroin addicts.

Performance in a vigilance task and the associated neuroendocrine changes during the performance in the task were examined in healthy subjects and in three groups of male heroin-addicts both before undergoing rehabilitation programmes and at various intervals from withdrawal (5 days, 1 to 2 mon, and 3 to 48 mon, respectively). Plasma levels of ACTH, beta-endorphin (EP) and prolactin (PRL) were measured every 10 min before and during performance. In drug addicts, simple reaction times never showed any significant difference as compared to control values. Despite similar baseline levels, ACTH exhibited a markedly depressed response to psychological testing in drug-addicts as compared to controls. Whereas a three-fold increase in ACTH was observed in 'normal' subjects during the performance (from 17 to 54 ng/l), mean values from drug-addicts remained unchanged. EP levels showed a wide scatter of individual values and inconsistent time courses over performance testing: after short-term abstinence, EP showed a three-fold increase over baseline control values but, contrary to what seen in 'normal' subjects, no changes over time were recorded. After long-term abstinence, basal EP was close to control values, but its increase during the testing period was still blunted. PRL levels decreased over the testing period both in controls and in heroin addicts. Thus, despite the lack of obvious signs of neurotoxicity, drug abusers show neuroendocrine changes consistent with a long-lasting selective impairment of the hypothalamic modulation of pituitary secretion.

Neurobehavioral and neuroendocrine effects of occupational exposure to perchloroethylene.

The hypothesis that long-term low-level exposure to perchloroethylene (PERC) may impair the dopaminergic control of prolactin (PRL) secretion and negatively affect neurobehavioral performance, was tested in a cross-sectional survey of dry-cleaners. Sixty female workers exposed to PERC in dry-cleaning shops and thirty controls recruited in a cleaning plant not using solvents were examined. PERC air concentration during four-hour random periods varied from 1 to 67 ppm (median 15 ppm). PERC blood levels ranged 12-864 mg/l (median 145 mg/l). A set of tests from a computer-based performance evaluation system was administered, including Finger Tapping with both dominant and non-dominant hands, Simple Reaction Times, Digit Symbol, and Shape Comparison in two different versions constructed to test Vigilance and the response to moderate stress, respectively. During the proliferative phase of the menstrual cycle, PERC-exposed workers showed increased serum PRL (12.1 +/- 6.7 ng/ml) as compared to their matched controls (7.4 +/- 3.1 ng/ml, p less than 0.001). Prolonged reaction times were also observed in all tests. However, neither the duration of exposure nor air and blood PERC concentrations were significantly correlated with performance. Nor were exposure variables associated with the increased PRL levels.