IP-10 Is an Early Diagnostic Marker for Identification of Late-Onset Bacterial Infection in Preterm Infants

Abstract

Very low birth weight (VLBW) infants with suspected late-onset infection requiring sepsis screening were enrolled in a prospective study to evaluate the diagnostic utilities of a comprehensive panel of key chemokines and cytokines, both individually and in combination, to identify diagnostic markers for early recognition of bacterial sepsis and necrotizing enterocolitis (NEC). Plasma chemokines interleukin (IL)-8, interferon-␥-inducible protein 10 (IP-10), monokine induced by interferon-␥ (MIG), monocyte chemoattractant protein 1 (MCP-1), growth-related oncogene-␣ (GRO-␣), and regulated upon activation of normal T cell expressed and secreted (RAN-TES) and cytokines IL-1␤, IL-6, IL-10, IL-12p70, and tumor necrosis factor ␣ (TNF-␣) were measured at the onset of sepsis (0 h) and 24 h later. Of 155 suspected infection episodes, 44 were classified as infected. Concentrations of all studied inflammatory mediators (except IL-1␤ and RANTES) were significantly higher in the infected than in the noninfected group at 0 h, but the levels decreased precipitously by 24 h. IP-10 with a plasma cutoff concentration Ն1250 pg/mL could identify all septicemic and NEC cases and had the highest overall sensitivity (93%) and specificity (89%) at 0 h. We conclude that preterm infants have the ability to induce a robust chemokine and cytokine response during sepsis, and IP-10 is a sensitive early marker of infection. and NEC are important risk factors that predispose to increased morbidity and mortality in preterm VLBW infants (1-4). A recent multicenter survey suggested that 21% of VLBW infants who survived Ͼ72 h of age had at least one episode of septicemia (1). Preterm infants who developed NEC had threefold increased risk of mortality (4). As the immunologic defense of preterm infants is considered to be immature and/or deficient (5), this category of patients is particularly vulnerable to developing severe and opportunistic infections in the immediate postnatal period (1,3,4). However, early warning signs and symptoms of systemic infection and NEC are often nonspecific and inconspicuous and can easily be confused with noninfective causes such as apnea of prematurity, gastrointestinal dysmotility, and acute exacerbation of bronchopulmonary dysplasia (6 -8). Thus, early identification of infants with bacterial sepsis and NEC has been recognized to be a major diagnostic challenge (7,8).Exposure to microorganisms and their derived products triggers a rapid and coordinated sequence of host reactions resulting in recruitment of leukocytes into areas of inflammation or sites of microbial invasion (9 -12). The regulation and trafficking of leukocytes into specific body tissues are principally controlled by chemoattractant cytokines or chemokines (10). The activation of leukocytes coupled with interaction of pro-and anti-inflammatory cytokines can influence the orchestration of the anti-infectious process and the magnitude of tissue damage and ultimately can determine the outcome of infection (13-16). Up-regulation (or down-regula...

Inflammatory molecules expression pattern for identifying pathogen species in febrile patient serum

“…Higher levels of IP-10 may be detected in sepsis, severe sepsis and septic shock groups compared with systemic inflammatory response syndrome (37). High levels of IP-10 have previously been detected in preterm infants with bacterial infection (12). Although bacterial and viral infection induce IP-10 level, the highest levels of IP-10 in the present study were observed among influenza virus, culture-negative and culture-positive groups (data not shown).…”

“…Culture-negative state is a commonly observed in patients diagnosed with sepsis (11)(12)(13)(14)(15). In the present study, serum CRP levels and WBC counts were sensitive and reliable indexes for distinguishing bacterial infection from viral infection.…”

“…As a host immune system recognizes pathogens and induces production of inflammatory molecules to resist pathogens, numerous cytokines and chemokines are used as biomarkers in laboratory research for the diagnosis and prognostic prediction of infectious diseases (5)(6)(7)(8)(9)(10)(11)(12)(13). For example, studies have shown that inflammatory cytokines levels are altered as a result of a variety of infections, including interleukin (IL)-1, IL-6, IL-10, IL-13, IL-18 and tumor necrosis factor-alpha (TNF-α) (5)(6)(7)(8).…”

“…Elevating plasma concentration of cytokines such as IL-6 and IL-10 may serve as a diagnostic marker of sepsis and is correlated with severity and survival of sepsis patients (9,10). In addition, certain chemokines, such as Regulated on Activation, Normal T cell Expressed and Secreted (RANTES), interferon-gamma-inducible protein 10 (IP-10) and CXCL8/IL-8, are associated with sepsis (11)(12)(13). These markers may provide important information for the early diagnosis of diseases.…”

IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions

“…A series of papers have demonstrated that unstimulated IP-10 levels in blood or plasma are increased with infection and disease, such as TB [101][102][103][104], hepatitis C viral infection [105][106][107] and bacteremia [108][109][110]. IP-10 is produced at the site of inflammation and the levels in the blood appear to correlate with the extent of the inflammatory process.…”