Immune deviation towards a Th1 response results in tumour/graft rejection involving IgG production, cytotoxic T lymphocytes, natural killer cells and macrophage activation. Conversely, deviation towards a Th2 response facilitates graft tolerance or tumourogenesis. Here, we investigated the involvement of protease-activated receptor-2 (PAR₂) in Th1/Th2 responses associated with skin allograft rejection, tumourogenesis and autoimmunity. Skin allografts were performed on C57 Bl/6 mice (anaesthetised with 100mg/kg ketamine and 15mg/kg xylazine) with donor 10mm diameter full skin thickness allografts obtained from Balb/c mice. The mice then received 0.2ml sc injections of either saline (vehicle) or SLIGRL (1.5mg/kg), daily, over a 14 day period. SLIGRL caused fewer animals to reject their grafts at day 10. In addition, SLIGRL-treated animals with accepted skin grafts demonstrated a significant (p<0.05) decrease in plasma IgG levels compared to saline controls whereas there was no difference in plasma IgE levels between treatments, at both days 5 and 10. IFN-γ and IL-10 release from isolated splenocytes were measured as markers of Th1 and Th2 responses, respectively. SLIGRL treatment did not affect IL-10 release, however, IFN-γ release significantly (p<0.01) decreased at day five, compared to control treated animals. Based on this study, we conclude that PAR₂ down-regulates Th1 immunological responses in a skin allograft model. We are currently investigating the role for PAR₂ in tumourogenesis and experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). To date, preliminary data indicates that sc SLIGRL does not affect growth of both melanoma and colon carcinoma in vivo as has been suggested to occur in in vitro studies (Yada et al. 2005, Nishibori et al. 2005). No data is available as yet for the EAE study. We predict that PAR₂ dependent inhibition of Th1 phenotype will prevent EAE. Conclusions to date are difficult, although predictions are sc SLIGRL may down-regulate Th1 immunological responses. This may be beneficial in the situation of a transplant or in autoimmune diseases such as MS.