Involvement of the spleen in the anti-prion activity of hydroxypropyl methylcellulose in mice

Abstract Prion diseases are a unique group of fatal infectious neurodegenerative disorders. Previously, we reported that hydroxypropyl methylcellulose (HPMC) exerts long-term anti-prion activity in prion-infected rodents after a single peripheral administration, but the mechanism of action is not well understood. Interestingly, the distribution of HPMC in mice partially resembles that of peripheral pathogenic prions, since peripherally administered HPMC remains in the spleen and lymphoid tissues for a long period. Here, we characterized the anti-prion activity of HPMC in relation to the spleen in mice. We found that the anti-prion activity of HPMC was attenuated in mice splenectomized after intracerebral prion infection, but enhanced in mice preinflamed with thioglycolate. Furthermore, the quantity of HPMC accumulated in the spleen significantly increased in mice treated with thioglycolate. Conversely, no attenuation of the anti-prion activity of HPMC was observed in mice when other HPMC-retained organs were removed. These findings reinforce the significance of spleen in therapeutic development and suggest that spleen-associated factors are involved in the anti-prion activity of HPMC.