Interleukin-2 deficit in hemodialysis patients. Role of prostaglandins.
Uremic patients suffer from various immunological alterations, whose pathogenesis is still unknown. Here, we studied 37 hemodialysis patients in order to investigate the role of prostaglandins (PGs) in uremic immunological deficiency, specifically in relation to interleukin-2 (IL-2) synthesis. We confirmed previous published data on deficient response to PHA in chronic renal failure patients (cpm, mean +/- SEM: 15,400 +/- 2,100 in uremics vs. 29,500 +/- 3,380 in controls, p < 0.04) and established a correlation between this deficiency and diminished IL-2 synthesis (r = 0.619, p < 0.05). The direct measurement of PGs in lymphocyte cultures showed greatly increased concentrations in the presence of uremic serum (US). We found that PGs synthesis can be inhibited by up to 80% if cultures are supplemented with indomethacin (IND--a cyclooxigenase inhibitor) or by removal of monocytes (producers of PGs). Both methods situated the uremic proliferative response within the normal range in cultures with FCS, and close to the normal range in cultures with US. We observed a deficit of IL-2 in hemodialysis patients (means +/- SD: 8,940 +/- 6,420 in uremics vs. 16,900 +/- 3,890 in controls). Addition of exogenous IL-2 normalized lymphocyte response even in US cultures, with no additive effect between PGs inhibition and exogenous IL-2 except in US cultures. It is suggested that IL-2 deficit of uremics depends, at least in part, on an increase in PGs synthesis induced by US.(ABSTRACT TRUNCATED AT 250 WORDS)
Glez-Gutiérrez
M
M
Nephrology Service, Hospital Marqués de Valdecilla, Santander, Spain.
de Francisco
A L
AL
Sanz de Castro
S
S
Ruiz
J C
JC
Prieto
M
M
García Fuentes
M
M
Arias
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood; D006435:Renal Dialysis; D013997:Time Factors; D014511:Uremia / Q000276:immunology / Q000628:therapy
D007376:Interleukin-2; D011453:Prostaglandins