Age-dependent levels of select immunological mediators in sera of healthy children

Abstract

Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-gamma), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-alpha, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-gamma and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-alpha, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-alpha, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.

FIG. 1

Age-related expression of immunological mediators in childhood (275 children 3 to 17 years of age) (Table 1). Normal values in adult donors are those provided by the suppliers of the respective kits. Note the remarkable degree of interindividual variability for most of the molecules.

FIG. 2

Levels (means with standard deviations) of IL-1RA, TNF-α, sICAM-1, sE-selectin, and sCD14 in serum in healthy children and normal adults (see the legend to Fig. 1). For these select molecules, the pooled childhood values (n = 275) were significantly different from the adulthood levels.

FIG. 3

Regression analysis and 95% confidence intervals of measured parameters at different ages. IL-1RA, IL-6, and TNF-α show not only higher values in children than in adults but also a characteristic pattern which resembles the rates of physical growth in childhood. Of note, sIL-2R, sE-selectin, and sCD14 undergo a progressive decline instead.