Production of lymphotoxin and tumor necrosis factor by human neonatal mononuclear cells.
Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytokines with many common biologic effects including antiviral activity and induction of fever and the acute phase response; despite common effects, they are molecularly distinct. Because neonates are unduly susceptible to viral infection and frequently fail to mount a febrile response to infection, we hypothesized that neonatal cells would produce less LT and TNF than adult cells. We analyzed LT and TNF production by blood mononuclear cells and purified T cells using Northern blot analysis to detect specific messenger ribonucleic acid and specific assays to detect LT and TNF protein in culture supernatants. Compared to LT, TNF messenger ribonucleic acid and protein were produced more rapidly both by total mononuclear cells and by T cells in response to mitogen stimulation. Although there was intersubject variability, adult and neonatal mononuclear cells and T cells (n = 6) produced similar amounts of LT and TNF messenger ribonucleic acid and protein with similar kinetics. In experiments with phytohemagglutinin-stimulated mononuclear cells from ten additional subjects, supernatant LT was somewhat greater in neonatal cultures (neonatal = 62.8 +/- 60.5, adult = 13.2 +/- 10.7 units/ml, p less than 0.05), and TNF was somewhat greater in adult cultures (neonatal = 708 +/- 429, adult = 1987 +/- 392 pg/ml, p less than 0.01) at 24 h; results at 48 h and 72 h were similar. Thus, neonatal MC produced as much or more LT than did adult MC. Although the decreased production of TNF by neonatal MC was statistically significant, these cells did produce substantial amounts of this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
English
B K
BK
Department of Pediatrics, University of Washington, Seattle.
Burchett
S K
SK
English
J D
JD
Ammann
A J
AJ
Wara
D W
DW
Wilson
C B
CB
D000328:Adult; D015152:Blotting, Northern; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008233:Lymphotoxin-alpha; D008934:Mitogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha