Inflammatory mediators of systemic inflammation in neonatal sepsis
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Inflammation Research
ORIGINAL RESEARCH PAPER
Inflammatory mediators of systemic inflammation in neonatal sepsis V. Sugitharini • A. Prema • E. Berla Thangam
Received: 21 January 2013 / Accepted: 21 August 2013 / Published online: 8 September 2013 Ó Springer Basel 2013
Abstract Objective and design Sepsis refers to severe systemic inflammation in response to invading pathogens. To understand the molecular events that initiate the systemic inflammatory response, various inflammatory mediators were analyzed in neonatal sepsis samples and compared with normal samples. Materials and methods We initially measured the levels of the various classical inflammatory mediators such as acute phase proteins [C-reactive protein (CRP) and procalcitonin (PCT)], granule-associated mediators (NE, MPO and NO), proinflammatory cytokines [tumour necrosis factor-a (TNFa), IL-1b and IL-6), antiinflammatory cytokines (IL-10 and IL-13) and chemokines [IL-8 and monocyte chemotactic protein (MCP-1)] and novel cytokines (IL-12/IL-23p40, IL-21 and IL-23) using ELISA. We also used the human inflammation antibody array membrane to profile the inflammatory proteins that are involved in neonatal sepsis. Results There were significantly higher levels of CRP (5.4 ± 0.70 mg/L), PCT (1.500 ± 0.2400 lg/L); NE (499.2 ± 22.01 lg/L), NO (54.22 ± 3.131 lM/L); TNFa (396.6 ± 37.40 pg/mL), IL-1b (445.3 ± 34.25 pg/mL), IL6 (320.9 ± 43.38 pg/mL); IL-8 (429.5 ± 64.08 pg/mL) MCP-1 (626.25 ± 88.91 pg/mL), IL-10 (81.80 ± 9.45 pg/
mL), IL-12/IL-23p40 (30.25 ± 0.6 pg/mL), IL-21 (8,263.3 ± 526.8 pg/mL) and IL-23 (6,083 ± 781.3 pg/mL) in neonates with sepsis compared to normal. The levels of MPO (21.20 ± 3.099 ng/mL) were downregulated, whereas there was no change in IL-13 (188.7 ± 10.63 pg/mL) levels in septic neonates when compared with normal. Using the human inflammation antibody array membrane, we detected the presence of 17 inflammatory proteins such as IL-3, IL6R, IL12p40, IL-16, TNFa, TNFb, TNF R1, chemokines I-309, IP-10 (IFN-c inducible protein 10), MCP-1, MCP-2, MIP 1b (macrophage inflammatory protein), MIP-1d, eotaxin-2, growth factors TGFb1 (transforming growth factor beta), PDGF (platelet derived growth factor), and cell adhesion molecule ICAM-1 (intracellular adhesion molecule) that were upregulated whereas RANTES which was downregulated in neonatal sepsis. Conclusion The simultaneous secretion and release of multiple mediators such as proinflammatory cytokines and chemokines, cell adhesion molecules, and growth factors were found to be involved in the initiation of systemic inflammation in neonatal sepsis. Therefore, measuring the concentration of multiple mediators may help in the early detection of neonatal sepsis and help to avoid unnecessary antibiotic treatment. Keywords Neonatal sepsis Inflammatory mediators Cytokines Acute phase proteins
Responsible Editor: Artur Bauhofer. V. Sugitharini E. Berla Thangam (&) Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Chennai 603203, Tamil Nadu, India e-mail:
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