Suppression of interleukin-1 beta and tumour necrosis factor-alpha biosynthesis by cadmium in in vitro activated human peripheral blood mononuclear cells.

Cadmium is a highly toxic element responsible for acute and chronic toxicity in man. There is evidence that cadmium induces pathophysiological effects by modulating components of the immune system. Cytokines are being increasingly recognized as essential mediators of normal and pathologic immune responses. Cadmium at concentrations varying from 1.0 x 10(-4) to 3.3 x 10(-6) M inhibited the phytohemagglutinin induced production of interleukin-1 beta and tumour necrosis factor-alpha, in in vitro activated human peripheral blood mononuclear cells. The messenger RNA levels of interleukin-1 beta and tumour necrosis factor-alpha were examined during a 24-h culture period, at different time points. The decreased messenger RNA levels at the time points of the maximum expression of interleukin-1 beta and tumour necrosis factor-alpha indicate that cadmium suppresses their production at the transcriptional level.

Prolonged Intermittent Chlorambucil Administration in B-Chronic Lymphocytic Leukemia: Experience from a Single Hematology Unit.

In the present study we investigated whether prolonged intermittent chlorambucil (Chl) administration is more effective for B-chronic lymphocytic leukemia (B-CLL) patients, compared to the traditional mode of shorter duration. One hundred and seventeen patients, entered the study, were scheduled to receive Chl orally for 10 days/mo, in a dose of 10 mg/daily, for a maximum period of 24 mo. Eighty-one patients (54M/27F), who had completed at least 10 mo of therapy were analyzed. Their median age was 60 yrs (30-80). Nine patients were stage A, 27 stage B and 45 stage C. Their median follow-up time from initiation of treatment was 40 mo (12-108). They received Chl for a median period of 18 mo (12-24). The overall response rate of our patients at six and 18 mo was similar (approximately 90%). However, there was a significant increase of complete responders at 18 mo compared to those at six mo of therapy (14/67 or 21% and 6/81 or 7.4%, respectively) (p < 0.025). Overall survival from the initiation of therapy according to the stage was as follows: stage A 50 mo, stage B 51 mo and stage C 33 mo. No statistically significant differences in survival among the three stages was found. No toxicity or increased incidence of second malignancy was observed except for one patient who was extremely sensitive to Chl and in whom therapy had to be discontinued temporarily. We concluded that at 18 mo of Chl administration the highest response had been achieved and that overall survival of stage C patients was similar to that at stages A and B.