Interleukin-6, C-reactive Protein, and Abnormal Cardiorespiratory Responses to Immunization in Premature Infants

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.