Serum Soluble ICAM-1, VCAM-1, L-Selectin, and P-Selectin Levels as Markers of Infection and their Relation to Clinical Severity in Neonatal Sepsis

ABSTRACT

Adhesion molecules may play a role in the evolution and severity of neonatal sepsis. The purposes of this study were to determine whether serum soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and P-selectin levels are useful tools in the diagnosis of proven sepsis in newborn infants, and whether their levels are related to the clinical severity of the disease. A cohort of 25 consecutive newborns meeting criteria for clinical sepsis, 10 hemoculture-negative (HC - ) and 15 hemoculture-positive (HC + ), were prospectively followed and compared with 12 healthy newborns (six ≤ 38 weeks of gestational age and six ≥ 39 weeks). Serum soluble (s)ICAM-1, sVCAM-1, sL-selectin, and sP-selectin concentrations were measured at the time of the septic workup, then followed by up to three determinations in each newborn every third day. The Score for Neonatal Acute Physiology (SNAP)-II severity was assessed at the moment of highest clinical severity of the disease. At the beginning of sepsis, sICAM-1 levels increased in both groups, being higher in HC + sepsis than in HC - ; sVCAM-1 only increased slightly in HC + sepsis. Soluble ICAM-1 levels were independently related to group of sepsis, and not to days of life. The best initial sICAM-1 cutoff level for diagnosing HC + neonatal sepsis was 274 μg/L. The highest sICAM-1 levels were positively correlated with SNAP-II scores. Soluble L-selectin and sP-selectin did not change. Soluble ICAM-1 levels increased in HC - and HC + sepsis, but concentrations > 274 μg/L suggest HC + sepsis. These levels were related to the clinical severity of the disease. Soluble VCAM-1 levels increased only slightly in HC + sepsis. Soluble L-selectin and sP-selectin did not change.

Adhesion molecules - newborn - sepsis - septic shock

REFERENCES

• 1 Larson R S, Springer T A. Structure and function of leukocyte integrins.  Immunol Rev. 1990;  114 181-217
• 2 Springer T A. Adhesion receptors of the immune system.  Nature. 1990;  346 425-427
• 3 Kourtis A P, Lee F K, Stoll B J. Soluble L-selectin, a marker of immune activation, in neonatal infection.  Clin Immunol. 2003;  109 224-228
• 4 Austgulen R, Arntzen K J, Haereid P E, Aag S, Dollner H. Infections in neonates delivered at term are associated with increased serum levels of ICAM-1 and E-selectin.  Acta Paediatr. 1997;  86 274-280
• 5 Butcher E C. Leukocyte-endothelial cell recognition. Three or more steps to specificity and diversity.  Cell. 1991;  67 1033-1036
• 6 Koch A E, Halloran M M, Haskell C J, Shah M R, Polverini P J. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1.  Nature. 1995;  376 517-519
• 7 Ramsay P L, Smith E OB, Hegemier S, Welty S E. Early clinical markers for the development of bronchopulmonary dysplasia: soluble E-selectin and ICAM-1.  Pediatrics. 1998;  102 927-932
• 8 Endo S, Inada K, Kasai T et al.. Levels of soluble adhesion molecules and cytokines in patients with septic multiple organ failure.  J Inflamm. 1995-1996;  46 212-219
• 9 Kuster H, Degitz K. Circulating ICAM-1 in neonatal sepsis.  Lancet. 1993;  341 506
• 10 Xanthou M, Fotopoulos S, Mouchtouri A, Lipsou N, Zika I, Sarafidou J. Inflammatory mediators in perinatal asphyxia and infection.  Acta Paediatr Suppl. 2002;  9 92-97
• 11 Dollner H, Vatten L, Austgulen R. Early diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6, soluble tumor necrosis factor receptors and soluble adhesion molecules.  J Clin Epidemiol. 2001;  54 1251-1257
• 12 Richardson D K, Corcoran J D, Escobar G J, Lee S K. for The Canadian NICU Network, The Kaiser Permanente Neonatal Minimum Data Set Wide Area Network, and The SNAP-II Study Group . SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores.  J Pediatr. 2001;  138 92-100
• 13 Phocas I, Sarandakou A, Giannaki G, Malamitsi-Puchner A, Rizos D, Zourlas P A. Soluble intercellular adhesion molecule-1 in newborn infants.  Eur J Pediatr. 1998;  157 153-156
• 14 Giannaki G, Xyni K, Rizos D, Phocas I. Comparative study of serum soluble VCAM-1 and ICAM-1 levels in the early neonatal period.  Acta Paediatr. 1999;  88 1413-1414
• 15 Smith C V, Hansen T N, Martin N E, McNicken H W, Elliot S J. Oxidant stress responses in premature infants during exposure to hyperoxia.  Pediatr Res. 1993;  34 360-365
• 16 Raynor B D, Parthasarthy S, Emory E K. Umbilical cord vascular cell adhesion molecule concentration following labor.  J Matern Fetal Med. 2000;  9 291-293
• 17 Malamitsi-Puchner A, Tziotis J, Mostakos G, Protonotariou E, Creatsas G. Adhesion molecules in early neonatal life.  Biol Neonate. 2000;  78 65-67
• 18 Distefano G, Betta P, Rodono A et al.. Concentrazioni sieriche di ICAM-1s in neonati a rischio di infeziones. Studio prospettico nelle prime due settimane di vita.  Pediatr Med Chir. 1997;  19 27-30
• 19 Whalen M J, Doughty L A, Carlos T M et al.. Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are increased in the plasma of children with sepsis-induced multiple organ failure.  Crit Care Med. 2000;  28 2600-2607
• 20 D'Alquen D, Kramer B W, Seidenspinner S et al.. Activation of umbilical cord endothelial cells and fetal inflammatory response in preterm infants with chorioamnionitis and funisitis.  Pediatr Res. 2005;  57 263-269
• 21 Darai E, Pocelet C, Soriano D et al.. Soluble intercellular adhesion molecule 1 in umbilical cord serum: potential for the diagnosis of neonatal infections.  Fetal Diagn Ther. 2002;  17 167-172
• 22 Smulian J C, Bhandari V, Campbell W A, Rodis J F, Vintzileos A M. Value of umbilical artery and vein levels of interleukin-6 and soluble intracellular adhesion molecule-1 as predictors of neonatal hematologic indices and suspected early sepsis.  J Matern Fetal Med. 1997;  6 254-259
• 23 Hansen A B, Verder H, Staun-Olsen P. Soluble intercellular adhesion molecule and C-reactive protein as early markers of infection in newborns.  J Perinat Med. 2000;  28 97-103
• 24 Edgar D, Gabriel V, Craig A, Wheeler D, Thomas M, Grant J. A low serum sICAM-1 level may assist in the exclusion of neonatal infection.  Biol Neonate. 2002;  81 105-108
• 25 Apostolou M, Dimitriou H, Kaleyias J et al.. Levels of soluble ICAM-1 in premature and full-term neonates with infection.  Mediators Inflamm. 2002;  11 95-98