Mechanism Of Sympathetic Regulation Of Systemic Inflammation In The Model Of Psoriatic Dermatitis Induced By Imiquimod

Background and Objective:Psoriasis is a chronic,recurrent and inflammatory skin disease,which is characterized by well-defined scaly erythema or plaques,and can also involve fingernails and joints.It has a long course of disease and is easy to recur,which brings heavy psychological and economic burden to patients and their families.At present,it is believed that the main causes of psoriasis include heredity,infection,immunity,endocrine and other factors,while lack of exercise,emotional tension and anxiety are important factors for the induction and aggravation of psoriasis.Among them,neuropsychiatric factors are important inducing factors that can not be ignored.Although the pathogenesis of psoriasis has not been fully elucidated so far,the following view has been widely accepted:cytokine network plays an important role in the pathogenesis of psoriasis and is a key factor in the persistence and progression of psoriatic lesions.Tumor necrosis factor-a(TNF--α),interleukin-23(IL-23)and interleukin-17(IL-17)are considered to be the main pro-inflammatory factors in the pathogenesis of psoriasis.In recent years,the emergence of biological agents has brought transformational progress to patients with psoriasis,but its wide application in psoriasis is limited because of its high price and unknown long-term complications.In addition,some patients do not respond well to biological agents.;even in patients with good response,long-term medication is needed to obtain long-term control of psoriasis,and there are some problems such as treatment resistance and relapse after drug withdrawal.This study proposes that splenic sympathetic signals are involved in splenic inflammatory activity after the occurrence of psoriasis,which leads to systemic inflammation.We hope to explore the neuroimmune mechanism of the occurrence and development of systemic inflammation in psoriasis and provide a new direction for the treatment and intervention of psoriatic systemic inflammation.Methods:1.To verify the local type 17 skin inflammation and systemic inflammation induced by imiquimod(IMQ)in the mouse model of psoriatic dermatitis.2.To explore the changes of skin lesions and spleen in psoriatic mouse model after 6hydroxydopamine blocking celiac sympathetic nerve.3.The changes of inflammatory cytokines and inflammatory cells were detected by RT q-PCR,Western Blot and flow cytometry to observe the local inflammation and systemic inflammation.Results:There are local type 17 skin inflammation and systemic inflammation in IMQ-induced mouse psoriasis model.After blocking the celiac sympathetic nerve,the skin inflammation and systemic inflammation of the psoriatic model mice were significantly relieved;the content of IL-6 protein in the skin lesions of the mice was decreased,but there was no difference in the expression of IL-6mRNA;the spleen swelling was greatly relieved,and the protein level and mRNA expression of inflammatory factors IL-6 and IL-1β in the spleen were also significantly downregulated;the number of neutrophils and monocyte-derived macrophages in the spleen decreased significantly.Conclusion:The mouse model of psoriasis induced by IMQ produces local type 17 skin inflammation and systemic inflammation,and the sympathetic nervous system is involved in this process.Blocking the celiac sympathetic nerve can relieve local and systemic inflammation by reducing the level of IL-6 protein in the skin lesions,the mRNA and protein expression of IL-6 and IL-1β in the spleen,and the infiltration of neutrophils and monocyte-derived macrophages in the spleen.