Emerging research reveals how IP-10, a microscopic immune messenger, could transform how we protect our smallest patients against deadly infections.
Diagnosing serious infections in neonates and young infants represents one of medicine's most persistent challenges. Unlike older children and adults, babies possess immature immune systems that respond differently to pathogens. Their signs of infection are often subtle and non-specific—lethargy, poor feeding, or temperature instability—that could indicate anything from a minor cold to devastating sepsis 7 .
This diagnostic delay creates a dangerous window where infections can spread unchecked. Doctors often must err on the side of caution, administering broad-spectrum antibiotics to potentially uninfected infants, contributing to the growing problem of antimicrobial resistance. The search for a rapid, accurate biomarker has therefore become something of a holy grail in neonatal medicine 5 .
Time needed for blood culture results
Of neonatal deaths caused by infections
Growing concern from overtreatment
IP-10 (Interferon gamma-induced protein 10), scientifically known as CXCL10, is a chemokine—a type of signaling protein that directs immune cells to sites of infection or inflammation. What makes IP-10 particularly special is its role as one of the first responders in the immune system's complex communication network 1 .
When the body detects invading bacteria, viruses, or other threats, certain cells release interferon-gamma, which in turn triggers the production of IP-10.
IP-10 acts as a homing beacon, guiding immune cells to the battle site, rising rapidly in the bloodstream during infection.
Researchers have discovered that IP-10 rises rapidly in the bloodstream during infection—often hours before conventional markers become elevated—making it an ideal early warning signal 4 . While IP-10 responds to various threats, studies reveal that it shows particularly strong elevation in bacterial infections, creating a distinctive signature that clinicians might use to distinguish bacterial invaders from other illnesses.
IP-10 rises rapidly—often hours before conventional markers like CRP become elevated—making it an ideal early warning signal for infections in neonates.
In 2007, a pivotal study published in Pediatric Research set out to systematically evaluate IP-10's potential for detecting late-onset infections in vulnerable preterm infants. The investigation, led by Ng and colleagues, marked a significant advancement in the field 1 3 .
The research team designed a prospective study enrolling very low birth weight infants who required sepsis evaluation due to suspected infection. They adopted a comprehensive approach, measuring not just IP-10 but a panel of inflammatory mediators including multiple chemokines and cytokines.
The findings were striking. At the onset of clinical symptoms, IP-10 levels were dramatically higher in infected infants compared to their non-infected counterparts.
Data adapted from Ng et al. Pediatric Research 2007 1
| Biomarker | Sensitivity (%) | Specificity (%) | Optimal Cutoff |
|---|---|---|---|
| IP-10 | 93 | 89 | ≥1250 pg/mL |
| IL-6 | 84 | 81 | Not specified |
| IL-8 | 79 | 76 | Not specified |
| CRP | 64 | 79 | >10 mg/L |
Data adapted from Ng et al. Pediatric Research 2007 1
| Patient Group | Typical IP-10 Level | Clinical Significance |
|---|---|---|
| Healthy neonates | Low (<1250 pg/mL) | Normal baseline |
| Bacterial sepsis | Very high (≥1250 pg/mL) | Strong indicator of infection |
| NEC cases | Very high (≥1250 pg/mL) | Indicator of intestinal pathology |
| Maternal COVID-19 exposure | Elevated (>26.1 pg/mL) | Sign of immune activation |
Interactive chart would display here comparing sensitivity and specificity of IP-10 against other biomarkers
Nearly two decades after the original discovery, a 2025 prospective multicenter study in sub-Saharan Africa provided powerful confirmation of IP-10's utility in a radically different healthcare setting. This research, conducted in Benin where sepsis burden is high and resources limited, introduced an important innovation: the CD74/IP-10 ratio 5 .
The African study demonstrated that this ratio had the best accuracy for diagnosing neonatal sepsis among all biomarkers tested, outperforming even traditional markers like procalcitonin. Furthermore, CD74 expression at birth showed remarkable accuracy in predicting which infants would ultimately succumb to sepsis, opening possibilities for early risk stratification in vulnerable populations 5 .
The recent pandemic unexpectedly provided additional insights into IP-10's behavior. A 2025 study revealed that neonates born to mothers with peripartum COVID-19 infection had significantly elevated IP-10 levels compared to controls (median 26.1 pg/mL versus 10.0 pg/mL), even when the babies themselves showed no signs of infection 6 8 .
This finding suggests that IP-10 responds not just to active infection but also to immune activation from maternal exposure, highlighting its sensitivity as an inflammatory marker. Despite these elevated levels, the exposed infants showed normal coagulation profiles, providing important clinical reassurance about the nature of this immune response 8 .
| Study | Population | Key Finding | Clinical Implication |
|---|---|---|---|
| Ng et al. (2007) | Preterm VLBW infants | IP-10 ≥1250 pg/mL detects sepsis with 93% sensitivity | Early diagnosis of late-onset infections |
| African Study (2025) | Sub-Saharan neonates | CD74/IP-10 ratio best diagnostic accuracy | Improved diagnosis in resource-limited settings |
| COVID-19 Study (2025) | Neonates of infected mothers | Elevated IP-10 without clinical infection | Marker of immune activation even without illness |
Studying a protein as subtle as IP-10 requires sophisticated laboratory tools. Here are the key components researchers use to measure and analyze this promising biomarker:
Antibody pairs specifically selected for their ability to bind to different parts of the IP-10 protein without interfering with each other.
Laboratory-created IP-10 of known concentration used to generate a standard curve, enabling precise quantification of unknown samples 4 .
An enzyme-linked molecule that binds to the detection antibodies and, when exposed to specific substrates, produces a color change measurable by spectrophotometer 4 .
Chemical solutions optimized for maintaining protein stability and ensuring accurate antibody-antigen interactions, particularly important with complex samples like plasma.
The accumulating evidence for IP-10's diagnostic capabilities raises exciting possibilities for clinical medicine. Researchers envision a future where rapid IP-10 testing could become part of standard emergency department protocols for febrile infants, potentially alongside traditional markers like CRP.
For neonatal intensive care units, IP-10 monitoring could offer an early warning system for the most vulnerable patients, detecting infections before clinical symptoms appear 5 .
The combination of IP-10 with other novel markers like CD74 might create a "sepsis signature" that could guide therapy more precisely than any single marker alone 5 .
Beyond diagnosis, IP-10 might help monitor treatment response, with falling levels indicating effective therapy and persistent elevation signaling the need for modification.
While technical and implementation challenges remain—including standardization across platforms and determining appropriate cutoff values for different populations—the scientific foundation is steadily building. What began as basic research into immune signaling molecules may soon give clinicians the power to listen to the immune system's whispers, transforming how we protect our smallest patients against their invisible foes.