Effect of dexamethasone on IL-2 and IL-3 production by mononuclear cells in neonates and adults.

Abstract

The effect of dexamethasone on interleukin 2 (IL-2) and interleukin 3 (IL-3) production by mononuclear cells in preterm and term infants and adults was evaluated. The capacity of mononuclear cells to produce these cytokines, in preterm infants with bronchopuhmonary dysplasia (BPD) and treated with dexamethasone, was compared with that before treatment.Twenty six preterm and 36 term neonates and 24 healthy adults were included in the study. Mononuclear cells isolated from neonatal cord blood (CBMC) and adult peripheral blood (PBMC) were stimulated with phytohaemagglutinin (PHA) in the absence or presence of dexamethasone at concentrations between 10-8M and 10-5M. IL-2 and IL-3 activities in the supernatant fluids were tested using bioassays. The in vivo effect ofthe drug on the production of these cytokines by PBMC in 10 preterms was determined before and 24 hours after dexamethasone administration (0.5 mglkglday).The production of both cytokines was inhibited in a dose dependent manner. A difference in the sensitivity of mononuclear cells to the inhibitory effect of the drug was found between neonatal cord blood cells and adult PBMC, the former being more sensitive. PBMC from preterm infants treated with dexamethasone for BPD produced significantly less IL-2 and IL-3 as early as 24 hours after the initiation of the treatment (43% and 31%; P<0.05, respectively).It is concluded that mononuclear cells from preterm and term neonates are more sensitive to the inhibitory effect of dexamethasone on IL-2 and IL-3 production. (Arch Dis Child 1996;75:F197-F201)

Effects of Dexamethasone on IL-1β, IL-6, and TNF-α Production by Mononuclear Cells of Newborns and Adults

“…In addition, CBMC have a unique cytokine profile when compared to PBMC. In accordance with our results, previous studies have demonstrated that blood MC or purified T cells from neonates are more sensitive to dexamethasone than cells from adults with regard to proliferation, IL-2 receptor expression [14], or IL-2 and IL-3 production [15]. Moreover, addition of dexamethasone to CBMC from preterm and term newborns at pharmacological doses induced maximal and moderate suppression of IL-2 and IL-3 production, respectively, whereas PBMC of adults were less affected [15].…”

“…In accordance with our results, previous studies have demonstrated that blood MC or purified T cells from neonates are more sensitive to dexamethasone than cells from adults with regard to proliferation, IL-2 receptor expression [14], or IL-2 and IL-3 production [15]. Moreover, addition of dexamethasone to CBMC from preterm and term newborns at pharmacological doses induced maximal and moderate suppression of IL-2 and IL-3 production, respectively, whereas PBMC of adults were less affected [15]. The current observation that PBMC incubated with a low concentration of dexamethasone (10 -7 M) responded in enhanced spontaneous secretion of IL-1ß and IL-6, whereas neonatal cells were not affected, is of interest, supporting the existence of differences between CBMC and PBMC.…”

“…This difference was not related to the affinity or binding capacity of labeled dexamethasone [12]. In a previous study [15], we have shown differences in the inhibitory effect of the drug on IL-2 and IL-3 production by cord blood mononuclear cells (CBMC) of preterm and term newborns and peripheral blood mononuclear cells (PBMC) of adults, the former being more sensitive. This phenomenon could be attributed to variance in the kinetics of production and/or absorption of these cytokines between newborns and adults, as has previously been shown for IL-2 [16].…”

Indomethacin and Ibuprofen Effect on IL-1ra Production by Mononuclear Cells of Preterm Newborns and Adults

“…It is shown in the present work that CBMC from preterm newborns differ from PBMC of adults in their sensitivity to the in vitro effect of IM and IB on IL-1ra production. These findings are supported by previous reports indicating that neonatal MC differ from those of the adult in cytokine profile, sensitivity to the inhibitory effect of dexamethasone and NSAIDs on the proliferative response, and cytokine production [13,14,[22][23][24][25][26][27]. It is possible that the variance in the response to NSAIDs between CBMC of preterms and PBMC of adults may be related to different levels of COX in the cells of the 2 age groups.…”

Effect of Dexamethasone on IL-10 and IL-12p40 Production in Newborns and Adults

“…Research on neonatal mononuclear cells, and particularly those of preterm newborns, has demonstrated that they are more sensitive to the inhibitory effect of DEX as for their proliferative response [21], and the production of IL-2, IL-3 [22], IL-6 and TNF-· induced by mitogens [23]. On the other hand, they are less sensitive to the effect of the drug on the spontaneous secretion of IL-1ß or IL-6 as compared to adult cells [23].…”