Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis.
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.
Flescher
E
E
Clinical Immunology Section, Audie L. Murphy Memorial Veterans Hospital, San Antonio, Texas.
Bowlin
T L
TL
Ballester
A
A
Houk
R
R
Talal
N
N
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D015317:Biogenic Polyamines / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis*; D007399:Interphase / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000502:physiology; D013095:Spermidine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology; D000097667:Polyamine Oxidase
D015317:Biogenic Polyamines; D006861:Hydrogen Peroxide; D007376:Interleukin-2; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011453:Prostaglandins; D013095:Spermidine; D000097667:Polyamine Oxidase