Effect of cefotaxime on cytokine production in newborns and adults in vitro.

The in vitro effect of cefotaxime on the production of interleukin (IL)-1beta, IL-2, IL-6 and tumor necrosis factor alpha (TNFalpha) was studied in term neonates and was compared with that of adults. The addition of cefotaxime caused a significant enhancement of IL-2 production by cells of both adults and neonates, and increased the secretion of TNFalpha by peripheral blood mononuclear cells (PBMC) of adults, whereas the synthesis of this cytokine by cord blood mononuclear cells (CBMC) of the newborns was not affected. In contrast with the described stimulatory effects of cefotaxime, this drug induced dose-dependent inhibition of the spontaneous and lipopolysaccharide (LPS)-induced IL-1beta production by cells of the two groups, but had no effect on the in vitro production of IL-6. These data suggest that cefotaxime, apart from its known antimicrobial activity, may modify the host immune response of both newborns and adults, via the alteration of cytokine production.

Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells.

The capacity of peripheral blood mononuclear cells (PBMC) to produce interleukin (IL) IL-1beta, IL-2, IL-3, IL-6, IL-10 and tumor necrosis factor-alpha (TNFalpha) was examined in term newborns with hyperbilirubinemia after 24 hours' exposure to phototherapy (wave length 425-475 nm). The results were compared with those from untreated neonates. Fifty newborns spontaneously delivered at term were included in the study. Blood samples were collected from 20 newborns before and 24 h after phototherapy. The control group consisted of 30 neonates examined on two consecutive days. PBMC isolated from blood samples were incubated in vitro for cytokine production. The concentration of cytokines in the supernatants was tested using ELISA kits (for IL-1beta, IL-6, IL-10 and TNFalpha), or by bioassays (for IL-2 and IL-3). Phototherapy caused a 70% increase in IL-2 secretion (123 +/- 27 vs 208 +/- 30 units/ml, P < 0.01) and 56% in IL-10 production (1.07 +/- 0.19 vs 1.67 +/- 0.33 ng/ml, P < 0. 03), whereas the spontaneous secretion of IL-1beta was reduced by 43% (13.7 +/- 2.3 vs 7.3 +/- 1.7 ng/ml, P < 0.02). In the control group the secretion of these cytokines was similar on the two consecutive days and did not differ significantly from secretion in the other group before phototherapy. On the other hand, lipopolysaccharide induced TNFalpha production was higher on the second day in the two groups of newborns irrespective of phototherapy (388 +/- 58 vs 683 +/- 88 pg/ml, P < 0.001, in the control group and 384 +/- 75 vs 588 +/- 91, P < 0.05, before and after phototherapy). The synthesis of IL-3 and IL-6 did not change significantly between the two days of the study. The results demonstrate that in addition to the well-known positive effect of phototherapy on the neonate serum bilirubin level, this treatment affects the function of the immune system in newborns via alterations in cytokine production.

Effects of dexamethasone on IL-1beta, IL-6, and TNF-alpha production by mononuclear cells of newborns and adults.

The effects of dexamethasone on the production of interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha were studied in preterm newborns, term infants, and adults. Twenty preterm and 22 term newborns and 30 healthy adults were included in the study. Mononuclear cells (MC) isolated from cord blood of newborns and peripheral blood of adults were incubated without or with lipopolysaccharide in the absence or presence of dexamethasone at concentrations between 10(-8) and 10(-5) M. The cytokine concentration in the supernatants was tested using enzyme-linked immunosorbent assay kits. Although a dose-dependent inhibition of the cytokine production was observed at pharmacological doses of dexamethasone in individuals of the three groups, differences in the intensity of the effect were observed between the groups. Spontaneous secretion of IL-1beta or IL-6 by MC of preterm neonates was less inhibited by dexamethasone as compared with cells from adults. In contrast, the inhibitory effect of the drug on lipopolysaccharide-induced IL-6 and tumor necrosis factor alpha production was more pronounced on neonatal cells. As for term newborns, MC were more sensitive to the inhibitory effect of the drug on LPS-induced IL-6 production than cells of adults. The results suggest that dexamethasone treatment of preterm newborns may affect cytokine production with a consequent modulation of the host's immune response.

Labor affects cytokine production in newborns.

PROBLEM: To investigate whether the mode of delivery or the drugs given to the mother during labor may affect the newborns' immune system. METHOD OF STUDY: Three groups of term newborns were included: A, spontaneously delivered with i.v. analgesia (n = 37); B, spontaneously delivered with epidural analgesia (n = 26); and C, delivered by cesarean section under general anesthesia (n = 29). Natural killer (NK) cell cytotoxicity, mitogenic response, and the capacity of peripheral blood mononuclear cells (PBMCs) to produce interleukin (IL)-1 beta, IL-2, IL-3, IL-6, and tumor necrosis factor (TNF)-alpha were examined. RESULTS: NK cell cytotoxicity increased significantly in all three groups of newborns on the second day of life. Decreased IL-2 production was observed in newborns delivered by cesarean section. Spontaneous IL-1 beta secretion was higher in newborns to mothers treated with epidural analgesia. Spontaneous IL-6 secretion was elevated in infants to mothers undergoing general anesthesia and surgery or epidural analgesia. TNF-alpha production was increased in newborns delivered by cesarean section. CONCLUSION: The immune response of the newborn is affected by the mode of delivery and/or drugs given to the mother during labor.

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

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 bronchopulmonary 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(-8)M and 10(-5)M. IL-2 and IL-3 activities in the supernatant fluids were tested using bioassays. The in vivo effect of the drug on the production of these cytokines by PBMC in 10 preterms was determined before and 24 hours after dexamethasone administration (0.5 mg/kg/day). 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.