Neuroimmunomodulation of in vivo anti-rotavirus humoral immune response

Neuropeptides and neurohormones (neurotransmitters) have been shown to modulate immune responses in vitro and in vivo. Since reproduction and lactation are regulated by neurohormones, we investigated whether neurohormones could enhance anti-rotavirus immunity in milk. Rotavirus-free mice were immunized orally with killed bovine rotavirus (BRV) and bred 6 weeks post-immunization. Post-whelping, each group of dams (ten mice/group) was given a single injection of prolactin (PRL), estrogen, PRL and estrogen or testosterone. The effects of neuropeptides, substance P (SP) and somatostatin (SS) on serum and lactogenic anti-rotavirus humoral immune responses were also investigated. The results revealed that in the groups given PRL or estrogen, anti-rotavirus antibody titers in milk and serum were enhanced. In contrast, testosterone had a negative effect on antibody titers. The administration of neuropeptide SP resulted in some enhancement of the lactogenic anti-rotavirus antibody titer at day 9 post-whelping whereas the opposite effect was observed following administration of SS. Prolactin given at 100 micrograms/mouse, on the day after whelping, gave optimum milk and serum antibody responses. Neurotransmitters potentiated immune responses to the weaker immunogenic proteins, VP4 and VP7 as well as to the strongly immunogenic VP6. In order to verify that the enhancement of anti-rotavirus antibody production was due to PRL and not to other factor(s), bromocriptine (BCR), a selective PRL inhibitor, was used as a control. Mice given BCR exhibited a drastic reduction in anti-rotavirus antibody in serum and milk. The role of neurotransmitters in the modulation of the lactogenic immune response and its significance in protection of neonates from enteric infections is discussed.