Dissimilar behavior of lymph cells in response to the action of aluminium. In vitro and in vivo studies.

In order to detect possible immunological effects of aluminum (Al) on lymph cells, mice were orally overloaded with pharmacological doses for 22 weeks. The in vitro response of lymph cells to mitogens (phytohemmaglutinin, PHA and concanavaline A, Con A) was examined at the end of the treatment. The chronic ingestion of Al affected the lymphatic nodes that were found to be 2- to 10-fold larger than those of the control mice. Concurrently, the in vitro proliferation of lymphatic node cells was found enhanced, while spleen cell cultures were unaffected. An acute direct action of Al on lymph cells from different sources was also examined. The blastogenic response to PHA of human peripheral lymphocytes was not disturbed by the presence of Al concentrations ranging from 0.09 to 900 microM. However, the response of mouse lymph cells was quite different, given that an Al dose-dependent inhibition was observed for lymphatic node cells, whereas for spleen cells the inhibition was only detected at Al concentrations higher than 90 microM. This work shows that Al might induce alterations in cell immune responses. The opposite results observed in mouse lymphatic node cells after in vitro and in vivo Al treatment, let us suggest that either the stimulating or suppressing effects of Al on the immune system might depend on the dose, route of administration and length of exposure, as well as on the cell population assayed.

Immunomodulatory activity of plasmatic substances.

In order to study circulating substances which could be involved in uremic immunodeficiency, the activity of plasma and plasmatic fractions of different molecular weight MW (A and B) from 12 patients with chronic renal failure (CRF) and 12 normal subjects (N) was assayed in vitro on PHA stimulated normal lymphocyte cultures. Plasma from CRF patients inhibited lymphoproliferation compared to normal plasma activity (mean +/- SD: 9,990 +/- 3,980 cpm vs. 22,163 +/- 3,054 cpm; p < 0.001). Nevertheless, the corresponding plasmatic fractions failed to induce similar effects. Both normal fractions showed inhibitory effects on proliferation while most of the CRF fractions allowed greater cellular proliferation than the former. The dose-response curves showed that all the normal fractions contained inhibitor(s) whose effect decreased with increasing dilution. Most of the B normal fractions also produced stimulatory effects when they were diluted between 1:5 and 1:25. Variable dose-response curves were obtained in the presence of CRF fractions. However, the lack of inhibitory activity in 9 of 12 patients and the stimulatory effects produced by several A-CRF fractions suggest qualitative differences between CRF and normal fractions. Present findings demonstrate inhibitory and stimulatory activities in the normal fractions which might be due to immunomodulator substances. Disorders in this immunomodulator system could be responsible for the immunodeficiency described in CRF patients.