Affiliation:
1. Department of Pediatrics, National University of Singapore, Singapore
2. Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA
Abstract
SUMMARY
Interleukin-13 (IL-13) is a known modulator of monocyte function, down-regulating monocyte surface markers such as CD14 and proinflammatory cytokines. We have shown previously that lymphocyte IL-13 gene expression was up-regulated during relapses in children with steroid-responsive nephrotic syndrome (SRNS). In this study, we examined the monocyte mRNA expression and lipopolysaccharide (LPS)-stimulated intracellular production of tumour necrosis factor-α (TNF-α) and IL-8 in children with SRNS during relapse and remission. Additionally, we investigated CD14 mRNA levels, CD14 surface expression and its soluble component (sCD14) in serum. Our results showed that the percentages of TNF-α positive monocytes following LPS stimulation were significantly lower in nephrotic children in relapse (64·4 ± 13·7%) compared to remission (81·6 ± 9·0%, P < 0·005). This was associated with down-regulation of CD14 mRNA, as well as both membrane and sCD14 in patients with nephrotic relapse (82·9 ± 10·1% and 1·23 ± 0·30 µg/ml, respectively) compared to remission (93·9 ± 3·2% and 1·77 ± 0·82 µg/ml, respectively) (P < 0·003). Although we demonstrated a decrease in LPS-stimulated intracellular production of TNF-α in monocytes from patients with nephrotic relapse, we were unable to show a concomitant decrease in mRNA expression during relapses. This could be explained by down-regulation of gene expression at the translational rather than transcriptional level. In conclusion, it is conceivable that up-regulation of T-cell IL-13 production in children with active nephrotic relapse was associated with suppression of monocyte CD14 expression, down-regulating pro-inflammatory cytokine production, and could account for the increased susceptibility to bacterial sepsis seen in nephrotic children in active relapse.
Publisher
Oxford University Press (OUP)
Subject
Immunology,Immunology and Allergy
Cited by
15 articles.
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