Dexamethasone

Dexamethasone (DEX) is a synthetic adrenocortical steroid that suppresses inflammation and normal immune responses. It is used systemically and locally to treat chronic inflammatory disorders, severe allergies, lymphomas, shock, CNS trauma, and to reduce high blood calcium levels. DEX has also been used in preterm infants to decrease morbidity and mortality associated with bronchopulmonary dysplasia and to prevent chronic lung disease consequent to neonatal respiratory distress syndrome (Mammel et al. 1983; Cummings et al. 1989). DEX therapy improved pulmonary and neurodevelopmental outcomes in very-low-birth weight infants at high risk for bronchopulmonary dysplasia (Cummings et al. 1989). DEX treatment also hastened weaning infants from mechanical ventilation; however infections occurred in a substantial proportion of patients studied by Mammel et al. (1983).

Bakker et al. (2000) investigated the effects that DEX treatment of neonatal rats has on susceptibility to and severity of experimental autoimmune encephalomyelitis (EAE). Newborn female Wistar rats were injected intraperitoneally (i.p.) with DEX on PND1, 2 and 3 with 0.5, 0.3, and 0.1|mg DEX/g/body wt, respectively. At 8 weeks of age, females exposed to DEX had decreased body weights compared with controls. These rats were injected s.c. in one hind footpad with 1.5 mg of guinea pig myelin basic protein (MBP) in incomplete Freunds adjuvant. Neurological aberrations were examined daily and graded 0 to 5 as follows: 0, no EAE; 0.5, loss of tip tail tonus; 1, loss of tail tonus; 2, partial tail paralysis; 3, complete tail paralysis; 4, hind limb paresis; and 5, hind limb paralysis. Disease severity was scored by observers in a blinded fashion. One week following MBP injection the first clinical signs of EAE appeared. The severity of EAE peaked at 13 days postimmunization and was significantly greater in DEX-treated rats compared to both saline and untreated cage control rats. Nine-week-old MBP-treated rats were injected with LPS and plasma corticosterone (CORT) levels were determined. Peak CORT levels were reduced in neonatal DEX-exposed versus control rats. These results are interesting in that an enhanced susceptibility to autoimmune disease has been correlated with reduction of the CORT response (Wick et al. 1993).

Peritoneal macrophages from 9- to 11-week-old neonatally exposed DEX female rats produced decreased levels of TNF-a and IL-1 a upon stimulation with LPS. The reduced cytokine responses by macrophages suggest that these macrophages may be less able to mount an adequate immune response to infections. Spleen cells, from these same rats, cultured with ConA expressed increased mRNA levels of the proinflammatory cytokines TNF-a and IFN-g. Taken together, these data suggest that neonatal exposure to DEX may be a risk factor for subsequent development of autoimmune disease and/or increased susceptibility to bacterial infections later in life (Bakker et al. 2000).

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