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Electronic Letters to:
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Electronic letters published:
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Prediction of sepsis – usefulness of cytometric measurements of cytokines and chemokines
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Barbara KrólakOlejnik, M.D., Pediatrician, Neonatologist Dept. of Perinatology and Gynecology in Zabrze, Silesian Medical University in Katowice, Poland, Igor Olejnik, M.D., Pediatrician,
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olejnik{at}olejnik.x.pl Barbara KrólakOlejnik, et al.
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The study of Ng PC et al. is a breakthrough in prediction of severe infection in very low birth weight (VLBW) infants. The prediction and diagnosis of sepsis in preterm infants, especially VLBW, are among the most serious problems in modern neonatology. Quick diagnosis is not easy because the symptoms of infection are often unspecific and subtle and may be similar to various noninfection conditions. The laboratory standard for determining sepsis is positive blood culture or positive cerebral spinal culture. Bacterial culture takes up 2-3 days and other presently used laboratory tests (white blood count, white blood indices, C-reactive protein) are not reliable for an early and absolute diagnosis (1). In recent years, cytokines, including chemokines, have been purposed as markers for diagnosis of infection in adults, children and infants (2,3,4,5). Proinflammatory cytokines stimulate secretion of many chemokines. Chemokines often act in concert with other cytokines to cause tissue infiltration by increasing a pool of given leukocytes and up- regulating particular adhesion molecules as well as increasing leukocytes responsiveness to chemokines. Within CXC chemokines subfamily IL-8, GRO-á, â, ă, NAP-2, GCP-2 and ENA-78 are homologous and certain ELR aminoacid motif is located within N terminal region of each molecule. They act by CXCR2 receptor and preferentially chemoattract neutrophils. In contrast, within CC chemokine superfamily, MCP-1, MIP-1á and RANTES act via the CCR2 receptor, which is expressed on monocytes, basophils and T cells, but is not expressed on neutrophils (6,7). An immature or not fully developed immunologic system predestines neonates to develop serious infections. New markers for sepsis that have been investigated for the last 10-15 years are not "the ideal diagnostic markers of infection” in neonatology (8). According to Ng PC serial measurements of infection markers should improve the diagnostic sensitivity of the tests. In addition, the combination of sensitive markers with late specific markers should enhance the diagnostic value of the mediators in identifying infections. There is a necessity to reduce unnecessary use of antibiotics and reduce the risk of emerging bacterial resistance in neonates. Markers should be used for early termination of antibiotic treatment in non- infected infants who usually receive at least 3 - day antibiotic therapy while waiting for bacterial culture. But it is extremely important to make an early diagnosis of sepsis because prompt antimicrobial therapy improves the outcome. Non-treated sepsis develops rapidly leading to septic shock, disseminated intravascular coagulation and other complications including death within hours. This most likely results from physiologic deficiency and immaturity of the immune system that diminishes preterm infants' inflammatory response, which is regulated, among other things, by cytokines and chemokines. Until now we have not had such ideal markers of infection in neonatology. Recent advances in flow cytometry allow quantitative, simultaneous measurement of a large panel of inflammatory mediators with a minimal volume of blood. It requires only 0.05 mL of plasma and therefore may be suitable for assessing pathophysiological processes of infection in neonates. The technology allows to obtain the values of the measured parameters within only four hours. The tertiary referral centers where preterm infants with severe infection are treated have the possibility to use cytometric analysis. The use of cytometric bead assay (CBA) kits is a quick, easy, low sample volume and sensitive method of measuring multiple plasma cytokines and chemokines (3). It may be recommended that we broaden their range with further cytokines, thus creating own sets out of flex sets. In the model of assessing concentration suggested by Ng PC et al., they obtained 100% sensitivity and 97% specificity of IL-10, IL-6 and RANTES for identifying infected preterm infants, who developed DIC. Random multicenter studies will allow the assessments of clinical usefulness of suggested studies. It would be particularly valuable to broaden the panel of studies by the chemokines helpful in diagnosing sepsis in adults such as GRO-á, MIP-1á i MIP-1â or ENA-78. This might allow using the model not only in VLBW infants with sepsis and DIC but also in preterm and term infants with sepsis. References 1. Gonzales BE, Mercado CK, Johnson L, Brodsky NL, Bhandari V. Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med 2003; 31: 60-8. 2. Dammann O, Philips TM, Allerd EN, O'Shea TM, Paneth M, Van Marter LJ et al. Mediators of fetal inflammation in extremely low gestational age newborns. Cytokine 2001; 13: 234-9. 3. Hodge G, Hodge S, Haslam R, Mcphee A, Sepulveda H, Morgan E et al. Rapid simultaneous measurement of multiple cytokine using 100 ěl sample volumes – association with neonatal sepsis. Clin Exp Immunol 2004; 137: 402-7. 4. Sullivan SE, Staba SL, Gersting JA, Hutson AD, Theriaque D, Christensen RD et al. Circulating concentrations of chemokines in cord blood, neonates and adults. Pediatr Res 2002; 51: 653-7. 5. Harris MC, D'Angio CT, Gallagher PR, Kaufman D, Evans J, Kilpatrick L. Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing enterocolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality. J Pediatr 2005; 147: 462-8. 6. Murdoch C, Finn A. Chemokine receptors and their role in inflammation and infectious diseases. Blood 2000; 95: 3032-3040. 7. Locati M, Bonecchi R, Corsi MM. Chemokines and their receptors. Role of specific clinical laboratory. Am J Clin Pathol 2005; 123(suppl 1): S1-S14. 8. Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed 2004; 89: F229-F35. |
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