Recurrent infections are common features in patients affected by propionic acidaemia (McKusick 232000) and methylmalonic acidaemia (McKusick 251000). Since these disorders are biochemically characterized by tissue accumulation of propionic acid and methylmalonic acid respectively, it is possible that these compounds may act as immunosuppressants. We therefore investigated the effect of propionate and methylmalonate on cellular growth of human peripheral lymphocytes stimulated in vitro by phytohaemagglutinin, concanavalin A and pokeweed mitogen, a recognized test of cellular immunocompetence. Lymphocytes were cultured in flat-bottomed 96-well microplates at 37 ;°C for 96 ;h (phytohaemagglutinin and concanavalin A) or 144 ;h (pokeweed mitogen) in the presence of one mitogen at different concentrations and of one acid added at doses of 1.0, 2.5 or 5.0 ;mM. Cell blastogenesis was measured by the incorporation of tritiated thymidine into cellular DNA and compared with that of identical cultures with no acid added (controls). A consistent and progressive inhibitory effect of propionic acid with increasing concentrations in culture was identified with all mitogens and was more pronounced with pokeweed mitogen. Lymphocyte blastogenesis was not altered in the presence of methylmalonic acid. The effect of propionate was observed only when the drug was added at the beginning (phytohaemagglutinin-activated) or until 24 ;h (concanavalin A- and pokeweed mitogen-activated) of culture. The viability of lymphocytes after treatment with the drug, as assessed by the Trypan Blue exclusion test, revealed no change when compared with the same untreated lymphocytes, indicating no lymphocytotoxic activity. In conclusion, propionic acid, which accumulates in tissues of patients with propionic acidaemia, causes ‘in vitro’ immunosuppression, which may be related to the recurrent infections characteristic of these patients.
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Research Article|
January 01 1999
Inhibition of mitogen-activated proliferation of human peripheral lymphocytes in vitro by propionic acid
Moacir WAJNER;
1Medical Genetics Unit, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil, and Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil
Correspondence: Professor M. Wajner.
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Kátia D. SANTOS;
Kátia D. SANTOS
1Medical Genetics Unit, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil, and Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil
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Jeanine L. SCHLOTTFELDT;
Jeanine L. SCHLOTTFELDT
1Medical Genetics Unit, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil, and Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil
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Maureen P. ROCHA;
Maureen P. ROCHA
1Medical Genetics Unit, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil, and Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil
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Clóvis M. D. WANNMACHER
Clóvis M. D. WANNMACHER
1Medical Genetics Unit, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil, and Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2600, CEP 90035–003, UFRGS Porto Alegre, RS, Brazil
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Publisher: Portland Press Ltd
Received:
July 20 1998
Revision Received:
August 12 1998
Accepted:
August 19 1998
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 1999
1999
Clin Sci (Lond) (1998) 96 (1): 99–103.
Article history
Received:
July 20 1998
Revision Received:
August 12 1998
Accepted:
August 19 1998
Citation
Moacir WAJNER, Kátia D. SANTOS, Jeanine L. SCHLOTTFELDT, Maureen P. ROCHA, Clóvis M. D. WANNMACHER; Inhibition of mitogen-activated proliferation of human peripheral lymphocytes in vitro by propionic acid. Clin Sci (Lond) 1 January 1998; 96 (1): 99–103. doi: https://doi.org/10.1042/cs0960099
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