Production of Lymphotoxin and Tumor Necrosis Factor by Human Neonatal Mononuclear Cells

English, B. Keith; Burchett, Sandra; English, Joey; Ammann, Arthur J.; Wara, Diane W.; Wilson, Christopher

doi:10.1203/00006450-198812000-00014

Cited by 86 publications

(32 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2 Because the passive uptake of cytokines by mucosal barriers during the neonatal period has not been elucidated, urinary levels of cytokines might reflect endogenous production by immune systems. Contrary to evidence suggesting that the production of several cytokines by neonatal T cells are either slightly (tumor necrosis factor-a) 25 or markedly reduced (IL-4, IL-6, IL-8, IL-10, and interferon-g), 26-29 IL-1b is known to be overproduced in preterm neonates and to be involved in excessive intestinal and systemic inflammation. 30 It has been noted that IL-1b initiates inflammatory cascades and enhances the expression of a powerful chemokine, IL-8, in immature intestinal cells.…”

Section: Discussionmentioning

confidence: 61%

Oropharyngeal Colostrum Administration in Extremely Premature Infants: An RCT

et al. 2015

View full text Add to dashboard Cite

To determine the immunologic effects of oropharyngeal colostrum administration in extremely premature infants. METHODS:We conducted a double-blind, randomized, placebo-controlled trial involving 48 preterm infants born before 28 weeks' gestation. Subjects received 0.2 mL of their mother's colostrum or sterile water via oropharyngeal route every 3 hours for 3 days beginning at 48 to 96 hours of life. To measure concentrations of secretory immunoglobulin A, lactoferrin, and several immune substances, urine and saliva were obtained during the first 24 hours of life and at 8 and 15 days. Clinical data during hospitalization were collected.RESULTS: Urinary levels of secretory immunoglobulin A at 1 week (71.4 vs 26.5 ng/g creatinine, P = .04) and 2 weeks (233.8 vs 48.3 ng/g creatinine, P = .006), and lactoferrin at 1 week (3.5 vs 0.9 mg/g creatinine, P = .01) were significantly higher in colostrum group. Urine interleukin-1b level was significantly lower in colostrum group at 2 weeks (55.3 vs 91.8 mg/g creatinine, P = .01). Salivary transforming growth factor-b1 (39.2 vs 69.7 mg/mL, P = .03) and interleukin-8 (1.2 vs 4.9 ng/mL, P = .04) were significantly lower at 2 weeks in colostrum group. A significant reduction in the incidence of clinical sepsis was noted in colostrum group (50% vs 92%, P = .003).CONCLUSIONS: This study suggests that oropharyngeal administration of colostrum may decrease clinical sepsis, inhibit secretion of pro-inflammatory cytokines, and increase levels of circulating immune-protective factors in extremely premature infants. Larger studies to confirm these findings are warranted. WHAT'S KNOWN ON THIS SUBJECT:Immunerelated bioactive proteins are highly concentrated in the colostrum of mothers who deliver preterm infants. Oropharyngeal administration was proposed as a safe and feasible alternative method of providing colostrum to immunocompromised premature infants. WHAT THIS STUDY ADDS:Oropharyngeally administered colostrum during the first few days of life increased urinary secretory immunoglobulin A and lactoferrin, decreased urinary interleukin-1b, reduced salivary transforming growth factor-b1 and interleukin-8, and reduced the occurrence of clinical sepsis in extremely premature infants.

show abstract

Section: Discussionmentioning

confidence: 61%

Oropharyngeal Colostrum Administration in Extremely Premature Infants: An RCT

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Although production of TNF-n and its effects on the host have been well characterized for adult animals, little is known about TNF-a in newborn animals. Production of TNF-a by fetal or neonatal cells in vitro has been reported as functionally equivalent to that of adult cells (35,36), but production in viva in response to infection is unknown. Similarly, the effect of TNFa on newborn PMN is unknown.…”

mentioning

confidence: 99%

Deficient Priming Activity of Newborn Cord Blood–Derived Polymorphonuclear Neutrophilic Granulocytes with Lipopolysaccharide and Tumor Necrosis Factor-α Triggered with Formyl-Methionyl-Leucyl-Phenylalanine

Bortolussi¹,

Howlett

Rajaraman³

et al. 1993

Pediatr Res

View full text Add to dashboard Cite

ABSTRACT. Newborn infants are more susceptible to bacterial infections than adults. This susceptibility has been attributed to defects in humoral and cellular activity. Host cellular activity can be modified by factors produced by bacteria or the host in response to infection. We assessed the effect of two factors associated with gramnegative bacterial infection, lipopolysaccharide (LPS) and TNF-a, on polymorphonuclear neutrophilic granulocytes (PMN) obtained from adult or newborns (umbilical cord blood). PILIN were primed in vitro with L P S (10 pg/L) or TNF-a (lo-' ILI) for 45 min and then assessed, using a chemiluminescence (CL) assay a s a n indicator of oxidative radical production with formyl-methionyl-leucyl-phenylalanine as the trigger for C L initiation. C L activity of unprimed P h I N was similar for adults and newborns (13.3 and 13.7 C L units, respectively). After priming with LPS, C L activity was increased to 43.4 C L units for P b I N from adults but to only 17.6 C L units for P b I N from newborns ( p < 0.001, adults versus newborn increment). Priming of P h I N with L P S was most effective when autologous plasma was present. Using FITC-conjugated L P S and a flow cytometry assay, we could demonstrate no difference between the binding affinity of L P S for adult and newborn PMN. IIowever, formyl-methionyl-leucyl-phenylalanine binding studies indicated that adult P h I N had a higher number of binding sites. TNF-a priming of newborn PILIN was also ineffective. Adult P M N increased CL activity by 3.9-fold when primed with TNF-a, whereas newborn PILIN increased by only 1.75-fold ( p < 0.005). This priming deficiency was not attributable to TNF-a receptors because phycoerythrin-conjugated TNF-a was associated with P h I N from adults and newborns equally. Thus, P h I N from newborns are not primed effectively in vitro with L P S or TNF-a. This defect may contribute to neonatal susceptibility to bacterial infection. (Pediatr Res 34: 243-248, 1993) Abbreviations PhIN, polymorphonuclear neutrophilic granulocyte IFN-y, interferon-y TNF-a, tumor necrosis factor-a

show abstract

“…In summary, cord blood lymphocytes not only produce a lesser amount of TNF (English et al, 39 Weatherstone and Rich, 40 present study), but they are also less susceptible to TNF-␣-induced apoptosis. The decreased susceptibility to TNF-␣-induced apoptosis in cord blood lymphocytes is associated with decreased expression of TNFR-I and certain adapter molecules, and with decreased expression and activity of both initiator and effector caspases.…”

Section: Discussionmentioning

confidence: 55%

“…However, cord blood mononuclear cells have been shown to produce lower amounts of TNF-␣ as compared to peripheral blood mononuclear cells. 39,40 The role of activation of NF-B in decreased TNF-␣-induced apoptosis in cord blood T cells remains to be examined.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, neonatal mononuclear cells produce significantly less TNF-␣ than peripheral blood mononuclear cells. 39,40 Therefore, in this study we compared TNF-␣-induced apoptosis between cord blood and peripheral blood lymphocytes. Our data show that decreased TNF-␣-induced apoptosis in cord blood T cell subsets is associated with decreased expression of TNFR-I, TRADD, and caspase 3, and decreased activity of both caspase 8 and caspase 3.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TNF-α-induced apoptosis in neonatal lymphocytes: TNFRp55 expression and downstream pathways of apoptosis

et al. 2000

View full text Add to dashboard Cite

Previously we have shown decreased Fas-mediated apoptosis in cord blood lymphocyte subsets. In this study, we compared tumor necrosis factor (TNF)-␣-induced apoptosis in T lymphocytes and their subsets between cord blood and peripheral blood from healthy young controls. The expression of TNF receptor I (TNFR-I) was assessed by flow cytometry and quantitative RT-PCR. The expression of adapter molecules TNF receptor-associated death domain (TRADD), Fasassociated death domain (FADD) and TNF-associated factor-2 (TRAF-2) and caspase 3 was analyzed by Western blotting. The activity of caspase 3 and caspase 8 was measured by colorimetric assay. The susceptibility of CD4 + and CD8 + T cells to TNF-␣-induced apoptosis was measured by terminal deoxytidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Both CD4 + and CD8 + T cell subsets from cord blood demonstrated decreased susceptibility to TNF-␣-induced apoptosis that was associated with decreased activation of both caspase 8 and caspase 3 as compared to T cell subsets in peripheral blood. Furthermore, expression of TNFR-I, TRADD and caspase 3 was decreased in cord blood lymphocytes as compared to peripheral blood lymphocytes. The significance of these observations is discussed. Genes and Immunity (2000) 1, 271-279.

show abstract

Production of Lymphotoxin and Tumor Necrosis Factor by Human Neonatal Mononuclear Cells

Cited by 86 publications

References 39 publications

Oropharyngeal Colostrum Administration in Extremely Premature Infants: An RCT

Oropharyngeal Colostrum Administration in Extremely Premature Infants: An RCT

Deficient Priming Activity of Newborn Cord Blood–Derived Polymorphonuclear Neutrophilic Granulocytes with Lipopolysaccharide and Tumor Necrosis Factor-α Triggered with Formyl-Methionyl-Leucyl-Phenylalanine

TNF-α-induced apoptosis in neonatal lymphocytes: TNFRp55 expression and downstream pathways of apoptosis

Contact Info

Product

Resources

About