Sympathetic nervous system stimulation could be directly involved in the pathophysiology of immune thrombocytopenia (ITP), according to an article recently published in the Journal of Thrombosis and Haemostasis.
“This is the first study to suggest that sympathetic regulation in the spleen is involved in the pathogenesis of ITP and supports the use of β2-[adrenergic receptor (AR)] agonist therapeutic strategies for ITP patients,” the authors wrote.
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This experimental study used wild-type control mice and C57BL/6 CD61 knockout ITP mice, and the researchers administered 6-hydroxydopamine to the ITP model mice to achieve chemical sympathectomy. They then analyzed immunological patterns before and after administering β2-AR agonists.
After confirming lower sympathetic activity among ITP mice that underwent the sympathectomy, the study found proportionally higher levels of type 1 T helper lymphocytes (Th1) and type 1 cytotoxic T cells (Tc1), as well as a lower percentage of regulatory T cells (Tregs).
Moreover, the gene expression profile varied accordingly, with significant upregulation of genes related to Th1, such as interferon gamma (INF) and interferon regulatory factor 8 (IRF8). Conversely, Foxp3 and CTLA4, genes widely associated with Tregs, showcased lower expression.
Interestingly, treating this mouse population with β2-AR agonists achieved a percentage of Tregs comparable to that prior to sympathectomy by day 7. Similarly, the platelet count was also restored by day 14.
Although the role of the sympathetic nervous system on hematopoiesis has been somewhat studied in the past, the effects reported in this study yield valuable information.
“A review summarizes β2-AR-mediated effects on immunity and demonstrates that stimulation of the β2-AR-cAMP-protein kinase A pathway causes selective suppression of the Th1 response and activation of the Th2 response,” the researchers explained.
These results suggest a potential use of β2-AR agonists in treating ITP. Specifically, the authors propose bambuterol, a long-acting, selective β2 agonist whose safety profile is already known to be favorable. This medication is a prodrug that transforms into its active form, terbutaline, by the butyrylcholinesterase enzyme. It is already widely accepted as a treatment option for asthma.
Zhang GC, Wu YJ, Liu FQ, et al. β2-AR agonist corrects immune thrombocytopenia by reestablishing the homeostasis of T cell differentiation. J Thromb Haemost. Published online March 25, 2023. doi:10.1016/j.jtha.2023.02.030