Glucocorticoid effects on natural and humoral immunity in mallards.

Two studies were conducted to determine the effects of dexamethasone (DEX) on immune function in mallard ducks. Each day ducks were injected intramuscularly with DEX at doses ranging from 0.2-4.0 mg/kg for 28-30 days. Physiologic effects consistent with high dose glucocorticoid (GC) treatment were observed at the 4 mg/kg dose, and included significant body weight loss, lowered hematocrit, and elevated alanine aminotransferase (ALT) activity. At all doses, effects of DEX on the immune system were observed. When DEX was given at 0.2 mg/kg/day, significant suppression of primary IgG antibody titers to sheep erythrocytes (SRBC) was observed. At 1 mg/kg/day, primary IgM and secondary IgM and IgG titers were suppressed as well. These doses of DEX also produced significant elevation in natural killer cell (NKC) activity of peripheral blood mononuclear cells (PBMNC). Removal of adherent cells from the PBMNC prior to NKC assay eliminated the enhancement in NKC activity. Based on these results, it was postulated that the elevation in NKC activity may be due to suppression by DEX of monocyte production of prostaglandin-E2 (PGE-2) resulting in the release of NKC activity from the inhibitory effects of PGE-2. This hypothesis was supported by a measured decrease in PGE-2 production during the NKC assay by cells from DEX-treated birds. Furthermore, an enhanced NKC activity could be reproduced in vitro with the addition of indomethacin or DEX to NKC cultures containing adherent cells from PBMNC. Direct effects of DEX on nonadherent cell NKC activity and lymphocyte viability were only observed at high concentrations (10(-4) M) of DEX, while the phagocytic activity of adhered blood monocytes was inhibited at 10(-6) M DEX. The suppressed phagocytic activity may contribute to the suppressed antibody responses observed in DEX-treated birds. Together, these results support an indirect immunomodulatory effect of DEX on NKC activity and perhaps antibody responses in vivo via altered monocyte function in mallard ducks.