Abstract
As a possible factor responsible for reduced fever responses in the newborn, we measured plasma cytokine concentrations and cytokine production by neonatal monocytes after lipopolysaccharide or IL (interleukin)-1α stimulation in vitro and compared these data with those obtained from adult plasma and monocytes. Whole blood was collected from afebrile adults (n=12) and the umbilical cord of normal term infants (n=12). Plasma and peripheral blood monocytes were prepared by conventional techniques. Significantly lower concentrations of IL-1α, IL-1β (P<0.05,t-test) and IL-6 (P< 0.01,t-test) were found in the plasma of newborn babies compared with that of adults. There was no significant difference in plasma tumour necrosis factor (TNF) concentrations between the adults and newborn babies. Monocytes from newborn babies had the capacity to produce IL-1α and IL-1β as readily as adult cells after stimulation with lipopolysaccharide or IL-1α, and produced significantly lower concentrations of TNF and IL-6 than those produced by stimulated adult monocytes (P< 0.01, ANOVA). Our results suggest that the reduced production of IL-6 by monocytes of the newborn during infection could be partly responsible for attenuated fever responses observed in the neonate.
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References
Blatteis CM, Smith KA (1979) Hypothalamic sensitivity to leukocytic pyrogen of adult and newborn guinea-pigs. J Physiol (Lond) 296:177–192
Bülow G-U v, Puren AJ, Savage N (1992) Interleukin-1 from baboon peripheral blood monocytes: altered response to endotoxin (lipopolysaccharide) andStaphylococcus aureus stimulation compared with human monocytes. Eur J Cell Biol 59:458–463
Cannon JG, Tompkins RG, Gelfand JA, Michie HR, Stanford GG, Meer JWM van der, Endres S, Lonnemann G, Corsetti J, Chernow B, Wilmore DW, Wolff SM, Burke JF, Dinarello CA (1990) Circulating IL-1 and TNF in septic shock and experimental endotoxin fever. J Infect Dis 161:79–84
Christensen RD, Hill HR, Rothstein G (1983) Granulocytic stem cell (CFUc) proliferation in experimental group B streptococcal sepsis. Pediatr Res 17:278–280
Craig WS (1963) The early detection of pyrexia in the newborn. Arch Dis Child 38:29–39
Dinarello CA, Shparber M, Kent EF, Wolff SM (1981) Production of leukocytic pyrogen from phagocytes of neonates. J Infect Dis 144:337–343
Dinarello CD, Cannon JG, Wolff SM (1988) New concepts on the pathogenesis of fever. Rev Infect Dis 10:168–189
Dinarello CA, Cannon JG, Mancilla J, Bishai I, Lees J, Coceani F (1991) Interleukin-6 as an endogenous pyrogen: induction of prostaglandin E2 in brain but not in peripheral blood mononuclear cells. Brain Res 562:199–206
English BK, Burchett SK, English JD, Ammann AJ, Wara DW, Wilson CB (1988) Production of lymphotoxins and tumor necrosis factor by human neonatal mononuclear cells. Pediatr Res 24:717–722
Glantz SA (1987) Primer of biostatistics, 2nd edn. McGrawHill, New York
Goelst K, Mitchell D, Laburn H (1992) Fever responses in newborn lambs. Pflügers Arch 421:299–301
Hellon R, Townsend Y, Laburn HP, Mitchell D (1991) Mechanisms of fever. In: Schonbaum E, Lomax P (eds) Thermoregulation: pathology, pharmacology and therapy. Pergamon, New York, pp 19–54
Kasting NW, Wilkinson MF (1987) Vasopressin as an endogenous antipyretic in the newborn. Biol Neonate 51:249–254
Khoruts A, Stahnke L, McClain CJ, Logan G, Allen JI (1991) Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients. Hepatology 13:267–276
Kluger MJ (1991) Fever: Role of pyrogens and cryogens. Physiol Rev 71:93–127
Kutteh WH, Rainey WE, Beutler B, Carr BK (1991) Tumor necrosis factor-alpha and interleukin-1 beta production by human fetal Kupffer cells. Am J Obstet Gynecol 165:112–120
Liechty KW, Koenig JM, Mitchell MD, Romero R, Christensen RD (1991) Production of interleukin-6 by fetal and maternal cells in vivo during intra-amniotic infection and in vitro after stimulation with interleukin-1. Pediatr Res 29:1–4
Long NC, Kunkel SL, Vander AJ, Kluger MJ (1990) Antiserum against TNF enhances LPS fever in the rat. Am J Obstet Gynecol 258:R332-R337
Long NC, Morimoto A, Nakamori T, Murakami N (1992) Systemic injection of TNF-alpha attenuates fever due to IL-1β and LPS in rats. Am J Physiol 263:R987-R991
Matsuzaki N, Saji F, Kameda T, Yashizaki K, Okada T, Sawai K, Tanizawa O (1990) In vitro and in vivo production of interleukin-6 by fetal mononuclear cells. Clin Immunol Immunopathol 55:305–314
Oppenheim JJ, Ruscetti W, Faltynek C (1991) Cytokine. In: Stites DP, Terr AI (eds) Basic and clinical immunology, 7th edn. Prentice-Hall, London, pp 78–100
Palexas GN, Puren A, Savage N, Welsh NA (1992) Serum interleukin (IL-1 beta) in patients with diffuse scleritis. Scand J Immunol 36 (Suppl 11): 171–172
Pillay V, Savage N, Laburn H (1993) Interleukin-1 receptor antagonist in newborn babies and pregnant women. Pflügers Arch 424:549–551
Pittman QJ, Cooper KE, Veale WL, Petten GR van (1974) Observations on the development of the febrile response to pyrogens in sheep. Clin Sci Mol Med 46:591–602
Riches P, Gooding R, Millar BC, Rowbottom AW (1992) Influence of collection and separation of blood samples on plasma IL-1, IL-6 and TNF-alpha concentrations. J Immunol Methods 153:125–131
Schibler KR, Liechty KW, White WL, Rothstein G, Christensen RD (1992) Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies in neonates. Pediatr Res 31:18–21
Tosato G, Jones KD (1990) Interleukin-1 induces interleukin-6 production in peripheral blood monocytes. Blood 75:1305–1310
Tosato G, Magrath IT, Koski IR, Dooley NJ, Blaese RM (1980) B cell differentiation and immunoregulatory T cell function in human cord blood. J Clin Invest 66:383–388
Vince G, Shorter S, Starkey P, Humphreys J, Clover L, Wilkins T, Sargent I, Redman C (1992) Localisation of tumor necrosis factor production in cells at the materno/fetal interface in human pregnancy. Clin Exp Immunol 88:174–180
Weatherstone KB, Rich EA (1989) Tumor necrosis factor/cachectin and interleukin-1 secretion by cord blood monocytes from premature and term neonates. Pediatr Res 25:342–346
Yachie A, Takano N, Yokoi T (1990) The capability of neonatal leukocytes to produce IL-6 on stimulation assessed by whole blood culture. Pediatr Res 27:227–233
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Pillay, V., Savage, N. & Laburn, H. Circulating cytokine concentrations and cytokine production by monocytes from newborn babies and adults. Pflügers Arch. 428, 197–201 (1994). https://doi.org/10.1007/BF00724497
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DOI: https://doi.org/10.1007/BF00724497