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Immunomodulatory activity of plasmatic substances
A M Lauricella1, H L Goldman, E J Massouh
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Insights
Chronic renal failure (CRF) plasma inhibits lymphocyte proliferation, but fractions show differing effects. CRF plasma fractions may have qualitative differences, potentially explaining uremic immunodeficiency.
Area of Science:
- Immunology
- Nephrology
- Biochemistry
Background:
- Uremic immunodeficiency is a recognized complication in patients with chronic renal failure (CRF).
- Circulating substances in CRF patients' plasma are hypothesized to contribute to immune dysfunction.
Purpose of the Study:
- To investigate the activity of plasma and plasma fractions from CRF patients on lymphocyte proliferation in vitro.
- To identify potential circulating factors responsible for uremic immunodeficiency.
Main Methods:
- Plasma and molecular weight (MW) fractions (A and B) from 12 CRF patients and 12 normal subjects were analyzed.
- In vitro assays were performed on PHA-stimulated normal lymphocyte cultures.
- Dose-response curves were evaluated for inhibitory and stimulatory effects.
Main Results:
- CRF plasma significantly inhibited lymphoproliferation compared to normal plasma (p < 0.001).
- CRF plasma fractions showed variable effects, with many exhibiting stimulatory activity, unlike normal fractions which were primarily inhibitory.
- Qualitative differences were observed between CRF and normal plasma fractions, suggesting altered immunomodulatory substances.
Conclusions:
- Normal plasma fractions contain immunomodulatory substances with both inhibitory and stimulatory activities.
- Disruptions in these immunomodulatory systems within CRF plasma may underlie the observed immunodeficiency in these patients.
Abstract:
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.