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Interleukin-6, C-reactive protein, and abnormal cardiorespiratory responses to immunization in premature infants
M Pourcyrous1, S B Korones, D Crouse
1Department of Pediatrics, University of Tennessee-Memphis, Memphis, Tennessee, USA.
Insights
Routine immunization with whole-cell pertussis vaccine (DTwP) in premature infants caused elevated IL-6 and CRP levels, mimicking bacterial infection. Acellular pertussis vaccine (DTaP) did not cause these elevations, suggesting DTwP
Area of Science:
- Neonatal immunology
- Vaccine response in premature infants
Background:
- Premature infants often exhibit abnormal clinical signs post-immunization.
- Elevated Interleukin-6 (IL-6) and C-reactive protein (CRP) are common after DTwP vaccination, mimicking bacterial infection.
- The necessity of antibiotic treatment for these post-vaccination inflammatory markers is questioned.
Purpose of the Study:
- To investigate the relationship between routine infant immunization and inflammatory markers (IL-6, CRP).
- To determine if the whole-cell pertussis component of DTwP is responsible for elevated IL-6 and CRP.
- To assess the occurrence of abnormal cardiorespiratory signs following immunization in premature infants.
Main Methods:
- Part 1: Prospectively evaluated 79 premature infants receiving DTwP, Hib, HBV, and IPV vaccines, monitoring IL-6 and CRP levels.
- Part 2: Studied 10 infants receiving DTaP followed by Hib, HBV, and IPV, with similar IL-6 and CRP monitoring.
- IL-6 and CRP levels were measured before and at intervals after immunization.
Main Results:
- In Part 1, 30% of infants developed abnormal cardiorespiratory signs; all but one showed elevated IL-6 and CRP post-DTwP.
- In Part 2, infants receiving DTaP did not exhibit elevated IL-6 or CRP levels.
- Abnormal cardiorespiratory signs in Part 1 were not correlated with the magnitude of IL-6/CRP elevation.
Conclusions:
- The whole-cell pertussis component in DTwP is responsible for IL-6 and CRP elevations in premature infants.
- DTaP vaccine does not elicit the same inflammatory response as DTwP.
- Premature infants require monitoring for approximately 48 hours post-immunization due to frequent cardiorespiratory events.
Objective:
We report our experience with routine immunization of 89 premature infants in the neonatal intensive care unit because 1) a substantial number of them developed abnormal clinical signs, and 2) all but one of those who received diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine responded with elevations of interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations that are otherwise characteristic of bacterial disease.
Methodology:
We hypothesized that the elevated IL-6 and CRP levels were solely a response to immunization and that treatment with antibiotics was not necessary. We performed this study in two consecutive parts. In part 1, we prospectively evaluated 79 consecutive premature infants who were immunized with DTwP, Haemophilus b conjugate vaccine, hepatitis B vaccine, and inactivated polio vaccine, (Hib, HBV, and IPV). IL-6 and CRP were determined before immunization and every 12 hours on three occasions after immunization. In part 2, we studied an additional 10 infants who received acellular pertussis vaccine (DTaP) and who, 2 days later, received Hib, HBV, and IPV immunization simultaneously. We followed the same schedule of IL-6 and CRP determinations as in part 1.
Results:
In part 1, 24 infants (30%) developed abnormal cardiorespiratory signs within 24 hours after immunization. CRP and IL-6 values rose to abnormal levels after immunization in all but one infant; that infant was later shown to have a T-cell abnormality. In part 2, 3 infants had abnormal cardiorespiratory signs after simultaneous immunization with Hib, HBV, and IPV, but not after DTaP. IL-6 and CRP levels remained normal in all 10 infants.
Conclusions:
Part 1 demonstrates clearly the temporal relationship between IL-6 and CRP increments after DTwP, Hib, HBV, and IPV vaccines. In part 2 (DTaP was substituted for DTwP), there were no elevations of IL-6 or CRP, thus indicating that whole-cell pertussis component of DTwP was responsible for IL-6 and CRP elevations. Abnormal cardiorespiratory signs occurred frequently after immunizations in part 1, but they were unrelated to the magnitude of IL-6 and CRP elevations. The frequency of cardiorespiratory difficulty and its occasional severity suggest a need to monitor premature infants for approximately 48 hours after routine immunization.