Prednisolone induces interleukin-18 expression in mononuclear blood and myeloid progenitor cells.
OBJECTIVE
Interleukin (IL)-18 is involved in host defense mechanisms and inflammatory diseases, among them rheumatoid arthritis (RA). High levels of IL-18 expression in RA joints are contrasted by reduced IL-18 expression in RA peripheral blood mononuclear cells (PBMC). Here, we investigated a putative IL-18 regulating role of corticosteroids.


METHODS
IL-18 transcript and protein levels in PBMC from untreated and prednisolone treated RA patients, and from healthy donors were assessed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting. IL-18 regulation was determined in PBMC and U937 cells upon exposure to prednisolone in vitro by RT-PCR and Northern Blot analysis, by ELISA in cell culture supernatants, and in transiently transfected THP-1 cells by IL-18 promoter activity luciferase assays.


RESULTS
In RA PBMC, IL-18 transcript levels were dose dependently restored, in parallel with administered prednisolone treatment, to subnormal levels. The corresponding intracellular IL-18 deposits in contrast were depleted. In cultured PBMC and promonocytic cell lines, prednisolone up-regulated IL-18 transcription in parallel with increasing the IL- 18 protein release into cell culture supernatants.


CONCLUSIONS
Prednisolone increases IL-18 expression and release in PBMC and monocytic cell lines.
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
D005938:Glucocorticoids; D020382:Interleukin-18; D012333:RNA, Messenger; D011239:Prednisolone