Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies of neonates.
Several deficiencies in antibacterial defense have been described in neonates. Among those best characterized are delayed maturation of B cells into antibody producing cells, deficient T-cell maturation, and delayed cycling of hematopoietic progenitor cells after an infectious challenge. No unifying theory has been forwarded, however, to explain the concomitance of these three developmental deficiencies. IL-6, a cytokine produced primarily by monocytes and macrophages in response to stimulation by IL-1, is involved in the regulation of these three processes. Thus, we postulated that defective production of IL-6 could be a mechanism underlying these immune deficiencies of neonates. Indeed, we observed that a peak production, cells of five term neonates produced only one half as much IL-6 (14 120 +/- 2590 pg IL-6/10(6) monocytes) as those of five adults (28 940 +/- 1680 pg, p less than 0.001). Peak production was lower still by monocytes of six preterm neonates (7190 +/- 1400 pg, p less than 0.001 versus term). Production of IL-6 protein was inhibited by actinomycin D and the IL-6 mRNA content of monocytes from neonates, as assessed by competitive polymerase chain reaction, was less than that of adult monocytes. We speculate that defective IL-6 transcription might underlie some of the defects in immune regulation observed in neonates.
Schibler
K R
KR
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
Liechty
K W
KW
White
W L
WL
Rothstein
G
G
Christensen
R D
RD
D000328:Adult; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn / Q000276:immunology*; D007234:Infant, Premature; D015850:Interleukin-6 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D015850:Interleukin-6; D012333:RNA, Messenger