Abstract:

Objective   To explore the role of L161982, one  prostaglandin E2-EP4 receptor antagonist, and its mechanism in rat experimental autoimmune neuritis (EAN). Methods   The rats were injected with bovine peripheral nerve myelin(BPM) antigen emulsion to prepare EAN model. Twenty-one Lewis rats were randomly divided into treatment group A, treatment group B and control group. Treatment group A were intraperitoneally injected daily with L161982(5mg/kg) from one day before immunization to the eighth day after immunization (immunization phase). Treatment group B were intraperitoneally injected daily with L161982(5mg/kg) from the fifth to sixteenth day after immunization (onset phase), and control group were intraperitoneally injected with the same volume of L161982 dissolvent. The effects were assessed in terms of appearance of clinical signs, clinical score, histopathology, and IFN-γ and IL-17 expressions in sciatic nerve sections, and the draining lymph nodes lymphocyte proliferative response was detected by cell counting kit-8(CCK-8). Results   Treatment group A and treatment group B displayed a significant delay in the onset of EAN (P＜0.05), a decreased inflammatory cell infiltration into the sciatic nerve(P＜0.05), decreased numbers of IFN-γ and IL-17 expressions in the sciatic nerve(P＜0.05), and reduced BPMstimulated T lymphocyte proliferative responses(P＜0.05) compared to the control group. Only treatment group A had decreased peak clinical score(P＜0.05). Conclusion   L161982 ameliorates the severity of EAN, presumably by moderating the over-expression of proinflammatory cytokines and suppressing self-reactive T lymphocyte proliferation. The immunization phase has a more significant therapeutic effect.

Key words: Neuritis; Rats; Experimental autoimmune; L161982; Interferon-γ;Prostaglandin E2 receptor;   Interleukin-17