Effect of dexamethasone on B7 regulation and T cell activation in neonates and adults

Abstract

The safety of dexamethasone for neonates has been questioned, partly because of its multiple unspecific effects on the immune system. Specific effects of dexamethasone on costimulatory and immune suppressive functions of neonatal compared with adult macrophages (MΦ) are not known. We evaluated the effect of dexamethasone on the expression and regulation of MΦ B7 family receptors (B7-1, CD80; B7-2, CD86) and on their ability to co-stimulate T cells. Cord blood macrophages (CBMΦ) and MΦ from healthy adults (PBMΦ) were isolated, and cell surface markers were phenotyped by flow cytometry. In tissue culture, cells were exposed to dexamethasone, interferon-γ (IFN-γ), cAMP, or a T cell mitogen (αCD3) and examined for their capacity to activate or destroy T cells. CBMΦ were less able to up-regulate CD80 and CD86 than PBMΦ (p < 0.05). Dexamethasone inhibited the up-regulation of CD80, CD86, and HLA-DR on PBMΦ and even more so on CBMΦ (p < 0.05 versus PBMΦ for CD80 and CD86). In the presence of dexamethasone, stimulation with αCD3 MAb enhanced cytotoxic functions of PMBMΦ and CBMΦ with an increase in deleted T cells, a reduced fraction of enlarged T cells, and an inhibition of T cell CD28 up-regulation, which again were more pronounced with CBMΦ (p < 0.05 versus PBMΦ). In conclusion, neonatal MΦ are exquisitely sensitive to the inhibitory effects of dexamethasone on B7 expression. Although perhaps producing the desired therapeutic effect, dexamethasone may do so in newborns at the expense of a near complete paralysis of MΦ-dependent T cell function. Copyright © 2005 International Pediatric Research Foundation, Inc.