The upregulation of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptid (PACAP) by prednisone led to a decrease in the expression of P53 protein as well as the rate of apoptosis in mesenteric lymph node lymphocytes. It also affected the expression of cytokines in a mouse model of immune thrombocytopenia (ITP).
These findings, which were published in the European Journal of Medical Research, suggest that prednisone may treat ITP by regulating intestinal immune function.
Read more about ITP pathophysiology
It was already known that VIP and PACAP play a role in modulating the immune system, which is dysfunctional in ITP, the researchers noted. However, their role in intestinal immune control was not clear, they added.
The aim of the present study was to explore the effect of prednisone, which is used to treat ITP, on the levels of platelet, VIP, and PACAP, and the regulatory system controlling intestinal immunity.
To address these questions, researchers led by Jun Wang used a mouse model. They divided the animals into 3 groups. They injected the animals in the second and third groups with antiplatelet serum to replicate the ITP model while they left the first group of animals untouched. They then treated the animals in the third group with prednisone 7 days later.
Before the injection of antiplatelet serum, there were no differences in platelet counts between the 3 groups of animals. However, on the 4th day of antiplatelet serum injection, the platelet count decreased and reached the lowest level on the 8th day. On the 12th day of injection, the platelet count recovered significantly in animals who were treated with prednisone and continued to rise on the 15th day.
The levels of VIP and PACAP significantly decreased in the brain, colon, and serum of animals injected with antiplatelet serum compared to those not injected. These levels then increased in the brain and colon of animals treated with prednisone. The levels of VIP also increased in the serum of treated animals.
p53 protein expression in the mesenteric lymph nodes of animals injected with antiplatelet serum significantly increased but then decreased again following prednisone treatment.
Finally, the levels of IFN- γ and IL-17A increased, and that of IL-4 and IL-10 decreased in animals injected with antiplatelet serum compared to those not injected. Prednisone treatment reduced levels of IFN- γ and IL-17A and increased levels of IL-4 and IL-10.
“Our experiments again demonstrate that VIP/PACAP is an important part of ITP pathogenesis,” the researchers concluded and said that future research could identify new agents targeting VIP/PACAP-mediated intestinal immune function that could be used to treat ITP.
Yan X, Zhang Y, Lang H, et al. Research on the mechanism of prednisone in the treatment of ITP via VIP/PACAP-mediated intestinal immune dysfunction. Eur J Med Res. Published online February 8, 2023. doi:10.1186/s40001-023-00987-x