Indomethacin and Ibuprofen Effect on IL-1ra Production by Mononuclear Cells of Preterm Newborns and Adults

The in vitro effect of indomethacin (IM) and ibuprofen (IB) on the production of the interleukin-1 receptor antagonist (IL-1ra) by cord blood mononuclear cells (CBMC) from preterm newborns was compared to that of peripheral blood mononuclear cells (PBMC) from adults. Mononuclear cells (MC) were incubated with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IM and IB. The level of IL-1ra in the supernatants was tested by ELISA. The results showed a lower ability of MC from preterm newborns to produce IL-1ra as compared with adult cells, supporting the assumption of neonatal immune cell immaturity. IM at pharmacological concentrations caused inhibition of IL-1ra secretion by PBMC from adults whereas IB suppressed the secretion of IL-1ra at higher concentrations only. At the same concentrations neither drug had an in vitro effect on the production of IL-1ra by CBMC of preterm newborns. In conclusion, the lower ability of CBMC of preterm newborns to produce IL-1ra in response to LPS and the absence of an IM and IB effect on the secretion of this cytokine by these cells as compared with PBMC of adults, suggest an underdevelopment of the immune response in preterm newborns.

[1]  L. Sirota,et al.  Effect of Dexamethasone on IL-10 and IL-12p40 Production in Newborns and Adults , 2001, Neonatology.

[2]  L. Sirota,et al.  CD14 Receptor Expression and Lipopolysaccharide-Induced Cytokine Production in Preterm and Term Neonates , 2001, Neonatology.

[3]  L. Sirota,et al.  Ibuprofen Affects Pro- and Anti-Inflammatory Cytokine Production by Mononuclear Cells of Preterm Newborns , 2001, Neonatology.

[4]  J. Weyler,et al.  A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. , 2000, The New England journal of medicine.

[5]  L. Sirota,et al.  Effect of indomethacin on IL‐1β, IL‐6 and TNFα production by mononuclear cells of preterm newborns and adults , 2000 .

[6]  C. Dinarello.  Is there an interleukin-1 genetic predisposition to developing severe sepsis? , 1999, Critical care medicine.

[7]  F. Noya,et al.  Deregulation of cyclooxygenase and nitric oxide synthase gene expression in the inflammatory cascade triggered by experimental group B streptococcal meningitis in the newborn brain and cerebral microvessels. , 1999, Seminars in perinatology.

[8]  J. Gierse,et al.  Kinetic basis for selective inhibition of cyclo-oxygenases. , 1999, The Biochemical journal.

[9]  F. Cabañas,et al.  Effect of the cyclo‐oxygenase blocker ibuprofen on cerebral blood volume and cerebral blood flow during normocarbia and hypercarbia in newborn piglets , 1999, Acta paediatrica.

[10]  K. Tanaka,et al.  The effects of nonsteroidal anti-inflammatory drugs on immune functions of human peripheral blood mononuclear cells. , 1998, Immunopharmacology.

[11]  M. Hurme,et al.  Gene polymorphisms of interleukins 1 and 10 in infectious and autoimmune diseases. , 1998, Annals of medicine.

[12]  T. Koshino,et al.  Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells. , 1998, European journal of pharmacology.

[13]  H. Matsuyuki,et al.  Effects of nonsteroidal anti-inflammatory drugs on interleukin-1 receptor antagonist production in cultured human peripheral blood mononuclear cells. , 1997, Prostaglandins.

[14]  B. Van Overmeire,et al.  Treatment of patent ductus arteriosus with ibuprofen , 1997, Archives of disease in childhood. Fetal and neonatal edition.

[15]  G. Bernard,et al.  The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. , 1997, The New England journal of medicine.

[16]  L. Sirota,et al.  Effect of dexamethasone on IL-2 and IL-3 production by mononuclear cells in neonates and adults. , 1996, Archives of disease in childhood. Fetal and neonatal edition.

[17]  S. Paul,et al.  Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[18]  H. Bada.  Routine indomethacin prophylaxis: has the time come? , 1996, Pediatrics.

[19]  K C Schneider,et al.  Neurodevelopmental outcome at 36 months' corrected age of preterm infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial. , 1996, Pediatrics.

[20]  C. Dinarello,et al.  Biologic basis for interleukin-1 in disease. , 1996, Blood.

[21]  A. Varvarigou,et al.  Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants. , 1996, JAMA.

[22]  I. Roberts,et al.  Ibuprofen treatment of patent ductus arteriosus , 1995, The Lancet.

[23]  G. Ramsay,et al.  Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group. , 1995, JAMA.

[24]  J. Sjölin,et al.  Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity. , 1995, The Journal of infectious diseases.

[25]  A. Kavelaars,et al.  Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells , 1995, European journal of immunology.

[26]  A. Okken,et al.  Increased Plasma Concentrations of Interleukin-1 Receptor Antagonist in Neonatal Sepsis , 1995, Pediatric Research.

[27]  F. Schildberg,et al.  Downregulation of proinflammatory cytokine release in whole blood from septic patients. , 1995, Blood.

[28]  R. Petty,et al.  Studies of human cord blood dendritic cells: evidence for functional immaturity. , 1994, Blood.

[29]  S. Lowry,et al.  Role of interleukin-1 and the therapeutic potential of interleukin-1 receptor antagonist in sepsis. , 1994, Circulatory shock.

[30]  C. McCall,et al.  Tolerance to endotoxin-induced expression of the interleukin-1 beta gene in blood neutrophils of humans with the sepsis syndrome. , 1993, The Journal of clinical investigation.

[31]  R. Zubler,et al.  Are cord blood B cells functionally mature? , 1991, Clinical and experimental immunology.

[32]  S. Abramson,et al.  The mechanisms of action of nonsteroidal antiinflammatory drugs. , 1989, Arthritis and rheumatism.

[33]  D. Santoli,et al.  Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism. , 1989, Journal of immunology.

[34]  L. Raisz,et al.  Biphasic effects of nonsteroidal anti-inflammatory drugs on prostaglandin production by cultured rat calvariae. , 1989, Prostaglandins.

[35]  Y. Bryson,et al.  Impaired production of gamma-interferon by newborn cells in vitro is due to a functionally immature macrophage. , 1985, Journal of immunology.

[36]  C. Leffler,et al.  Cerebral arteriolar dilation to hypoxia: role of prostanoids. , 1997, The American journal of physiology.

[37]  L. Ac.  Interleukin-1 receptor antagonist. , 1995, Critical reviews in immunology.

[38]  W. Arend.  Interleukin-1 receptor antagonist. , 1993, Advances in immunology.