Regulation of interleukin-2 and interferon-gamma gene expression in renal failure.
Regulated expression of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) genes, induced in cultured peripheral blood mononuclear cells from patients with end-stage renal disease on hemodialysis (HD; N = 13) or peritoneal dialysis (PD; N = 13), was compared to that of 32 normal donors. Culture conditions were chosen that measure the transient, phytohemagglutinin-induced expression of IL-2 and IFN-gamma messenger RNA (mRNA), as well the intactness of post-transcriptional and suppressor T cell-dependent mechanisms that control this expression. The latter was achieved by analyzing the superinduction of IL-2 and IFN-gamma mRNA occurring upon culture with cycloheximide or after low-dose gamma-irradiation, respectively. HD subjects showed a complete loss of inducibility of the IL-2 gene, concomitant with decreased inducibility of IFN-gamma mRNA. In PD subjects, by contrast, expression of IL-2 mRNA was as vigorous as in normal donors, while IFN-gamma mRNA was even more strongly inducible. This difference in gene inducibility is caused by a lack of T cell function in HD subjects. The defect in IL-2 gene expression in HD subjects, occurring most likely at transcription, may underly their impaired immune function.
Department of Molecular Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
L
L
Gerez
L
L
Madar
T
T
Shkolnik
B
B
Kristal
G
G
Arad
A
A
Reshef
A
A
Steinberger
M
M
Ketzinel
D
D
Sayar
S
S
Shasha
D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2; D007371:Interferon-gamma