The anthelmintic drug praziquantel promotes human Tr1 differentiation.

Praziquantel (PZQ) is an anthelminthic human and veterinary drug used to treat trematode and cestode worms. Changes in immune responses have been demonstrated in humans following curative PZQ treatment of schistosome infections. These changes have been attributed to the removal of immunosupressive worms and immune responses to parasite antigens exposed from dying worms. To date, there has been no study investigating the potential direct effect of PZQ on the host immune cells. Herein, we analyzed the effect of PZQ on human CD4+ T cells classically costimulated by CD3/CD28 or costimulated by the complement regulator CD46 to induce Type 1 regulatory T cells (Tr1). Our results show that PZQ enhanced T-cell proliferation, increased secretion of IL-17 and IL-10 but had no effect on secretion of GM-CSF or IFNγ. Moreover, PZQ increased the coexpression of CD49b and LAG-3, a hallmark of Tr1 cells, suggesting increased Tr1 differentiation. Indeed, supernatants from PZQ-treated cells were able to decrease bystander T-cell activation, and this was partly reduced when blocking IL-10. Hence, our study demonstrates that PZQ directly modulates human T-cell activation and promotes Tr1 differentiation, suggesting that PZQ may have immunomodulatory functions in parasite-unrelated human inflammatory diseases.

Coronal rhytidectomy in conjunction with deep plane walking sutures, modified Hotz-Celsus and lateral canthoplasty procedure in a dog with excessive brow droop.

This case report describes a unique technique of rhytidectomy in a Bloodhound to repair excessive brow folding and droop complicating underlying entropion. This case posed specific challenges due to the loose fascial plane connective tissue. A large circular area of coronal skin was excised, followed by placement of deep plane walking fixation sutures for cosmetic realignment and to alleviate brow droop. In addition, a modified Hotz-Celsus procedure and lateral canthoplasty were performed to address the primary entropion. The coronal rhytidectomy was considered a successful approach to repair excessive brow droop in this Bloodhound.