Prevention of immune dysfunction and vitamin E loss by dehydroepiandrosterone and melatonin supplementation during murine retrovirus infection

Abstract

Female C57BL/6 mice infected with the LP-BM5 leukaemia retrovirus developed murine acquired immune-deficiency syndrome (AIDS). Dehydroepiandrosterone (DHEA) and melatonin (MLT) modify immune dysfunction and prevent lipid peroxidation. We investigated whether DHEA and MLT could prevent immune dysfunction, excessive lipid peroxidation, and tissue vitamin E loss induced by retrovirus infection. Retrovirus infection inhibited the release of T helper 1 (Th1) cytokines, stimulated secretion of Th2 cytokines, increased hepatic lipid peroxidation, and induced vitamin E deficiency. Treatment with DHEA or MLT alone, as well as together, largely prevented the reduction of B- and T-cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. DHEA and MLT simultaneously reduced hepatic lipid peroxidation and prevented vitamin E loss. The use of DHEA plus MLT was more effective in preventing retrovirus-induced immune dysfunction than either DHEA or MLT alone. These results suggest that supplementation with DHEA and MLT may prevent cytokine dysregulation, lipid oxidation and tissue vitamin E loss induced by retrovirus infection. Similarly, hormone supplementation also modified immune function and increased tissue vitamin E levels in uninfected mice.

Figure 1

Effects of DHEA, MLT and DHEA+MLT on LPS-stimulated B-cell- and Con A-stimulated T-cell proliferation of splenocytes. Every sample from each mouse was measured in triplicate. The bars are the mean±SE for eight mice. Letters indicate significant differences at P < 0·05. (a) Compared with uninfected mice receiving the same treatment; (b) compared with their respective untreated controls; (c) compared with their respective DHEA-treated mice; (d) compared with their respective MLT-treated mice.

Figure 2

Effects of DHEA, MLT and DHEA+MLT on Th1 cytokine production by splenocytes. Every sample from each mouse was measured in triplicate. The bars are the mean±SE for eight mice. Letters indicate significant differences at P < 0·05. (a) Compared with uninfected mice receiving the same treatment; (b) compared with their respective untreated controls; (c) compared with their respective DHEA-treated mice; (d) compared with their respective MLT-treated mice.

Figure 3

Effects of DHEA, MLT and DHEA+MLT on Th2 cytokine production by splenocytes. Every sample from each mouse was measured in triplicate. The bars are the mean±SE for eight mice. Letters indicate significant differences at P < 0·05. (a) Compared with uninfected mice receiving the same treatment; (b) compared with their respective untreated controls; (c) compared with their respective DHEA-treated mice.

Figure 4

Effects of DHEA, MLT and DHEA+MLT on hepatic vitamin E concentrations and conjugated diene production. Every sample from each mouse was measured in triplicate. The bars are the mean±SE for eight mice. Letters indicate significant differences at P < 0·05. (a) Compared with uninfected mice receiving the same treatment; (b) compared with their respective untreated controls; (c) compared with their respective DHEA-treated mice; (d) compared with their respective MLT-treated mice.

Figure 5

Effects of DHEA, MLT and DHEA+MLT on hepatic phospholipid content and total cholesterol levels. Every sample from each mouse was measured in triplicate. The bars are the mean±SE for eight mice. Letters indicate significant differences at P < 0·05. (a) Compared with uninfected mice receiving the same treatment; (b) compared with their respective untreated controls; (c) compared with their respective DHEA-treated mice; (d) compared with their respective MLT-treated mice.