Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats

Major concern has emerged about the possible long term adverse effects of g lucocorticoid treatment, which is frequently used for the prevention of chr onic lung disease in preterm infants. Here we show that neonatal glucocorti coid treatment of rats increases the severity (p less than or equal to 0.01 ) and incidence (p less than or equal to 0.01) of the inflammatory autoimmu ne disease experimental autoimmune encephalomyelitis in adult life, In sear ch of possible mechanisms responsible for the increased susceptibility to e xperimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal asis and of immune tells in adult rats a fter neonatal glucocorticoid treatment. We observed that neonatal glucocort icoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p less than or equal to 0.001), Interestingly, LPS-stimulate d macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL- 1 beta in adult life than control rats (p less than or equal to 0.05), In a ddition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p < 0.01) and TNF-<beta> (p < 0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucoco rticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life, In view of the frequent clinical applica tion of glucocorticoids to preterm infants, our data demonstrate that neona tal glucocorticoid treatment may be a risk factor for the development of (a uto)immune disease in man.