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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Apr;83(4):1356–1362. doi: 10.1172/JCI114023

Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis.

E Flescher 1, T L Bowlin 1, A Ballester 1, R Houk 1, N Talal 1
PMCID: PMC303829  PMID: 2784801

Abstract

Polyamines downregulate immune reactivity. RA is associated with decreased IL 2 production. In this study, we present evidence to suggest that excessive polyamines can contribute to the IL 2 deficiency in RA. Blocking polyamine production with inhibitors of ornithine decarboxylase results in increased IL 2 production by RA PBMC. Moreover, polyamine oxidase (PAO) inhibitors and catalase also increase IL 2 production by RA PBMC. This effect of PAO inhibition is monocyte mediated. After 3 d in culture, RA PBMC produce three times more IL 2 than do normal PBMC. This rise is prevented by exogenous spermidine but only in the presence of monocytes. The concentration of polyamines in RA PBMC and synovial fluid MNC is 2-20-fold higher than in normal cells. Thus, polyamines and their oxidation products downregulate IL 2 production by RA PBMC and may account for the decreased T cell effector function seen in this disease.

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Selected References

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