Comparison of mannitol versus pertussis toxin to exacerbate active experimental autoimmune encephalomyelitis (EAE)

Experimental autoimmune encephalomyelitis (EAE) is a powerful and broadly used model to study multiple sclerosis (MS). Like most models, it has advantages and limitations; its advantages include that it can be induced in many species, the pathological mechanisms identified for EAE often overlap with MS, and it has been used for pre-clinical screening for therapeutics that are now used for individuals with MS. Further, there are many approaches for EAE induction, including active immunization with myelin proteins emulsified with immune adjuvants or passive transfer of EAE-specific T cells, allowing focus on the T cell-dependent aspects of disease. EAE also has its limitations, such as variability in incidence and severity. Use of additional adjuvants such as pertussis toxin (PTx) have been employed to hasten onset and exacerbate disease severity, but there also might be conditions under which PTx use would not be indicated, such as avoiding PTx-induced inhibition of Giα receptor signaling. Together these data demonstrate that further refinement of the model is needed, and we hypothesized that mannitol could serve as a PTx replacement since both mannitol and PTx can compromise the blood brain barrier (BBB). The objective of this study was to directly compare EAE induced with no additional adjuvants with EAE induced with intraperitoneal injections of PTx or ad libitum access to mannitol in the drinking water. Our data show that either PTx or mannitol exacerbated EAE disease demonstrating that mannitol treatment can be considered for active EAE induction in lieu of PTx.