| We measured changes in pro-inflammatory cytokines/chemokines(IFN-?,TNF-?,IL-17,MCP-1,IL-1,IL-8?IL-6) and the influence of anti-infl ammatory agents(CVF?Actemra?AAT) in immunosuppressed baboon r ecipients of pig grafts. For providing experimental basis that a combinati on of anti-inflammatory agents may be necessary to achieve long-term pi g graft survival in primates.Methods:(1)Baboons received an artery patch(n=8) from genetically-engi neered pigs(n=2 GTKO/h CD46/h ERCP or n=6 GTKO/h CD46). And trans genic express ion in donor p AEC was studied by flow cytometry.(2)baboo ns received either(A) no anti-inflammatory agent(n=2 GTKO/h CD46/h E RCP),(B) an interleukin-6 receptor antagonist(IL-6RA, n=2),(C) ?1-antitr ypsin(AAT, n=2)(D) cobra venom factor(CVF, n=2).(3)Draw blood fro m recipient before and after xenotransplantation, then isolation serum. Ser um samples were tested for IFN-?, IL-17, TNF-?, IL-1,MCP-1,IL-8,IL-6,CRP by using LEGENDplex Luminex kits.Results:(1)There was no express of Gal,but high express of CD46 and EPCR on h AEC.the same as GE-p AEC(1).There was no express of Gal and EPCR,but high express of CD46 on GE-p AEC(2).There was high express of Gal, but no express of CD46 and EPCR on the WT-p AEC(2)In CVF, AAT and no anti-inflammatory drugs group, serum CRP concentration increased rapidly in three days after operation, from less than 0.5mg/dl tomore than 2mg/dl, then slowly decreased to about 1.5mg/dl and remain stable. But in Actemra group,serum CRP concentration remain stable, less than 0.5mg/dl.(3)In 4groups,the serum IFN-? concentration nearly no change compare with preoperative, less than 20pg/ml,.but in group AAT,the serum IFN-?concentration is more than 20pg/ml in 30 th days and may have increased.(4)The concentration of serum IL-6 in CVF, AAT, Actemra group was not significantly increased, less than 50pg/ml. However, in no anti-inflammatory treatment group, serum IL-6 concentration increased rapidly within seven days after the operation, from 100pg/ml increased to about400mg/dl, then decreased slowly to about 250mg/dl and remained stable.(5)In the 4 experimental groups, serum TNFF-? concentration was not significantly increased, remained about 10pg/ml after operate.(6)In Actemra group, the serum concentration of IL-17 increased to about 160pg/ml rapidly in three days after operation,then decreased to about 25pg/ml,in AAT,CVF and no anti-inflammatory treatment group the concentration of IL-17 was the same as preoperative.(7)In the Actemra group, the serum IL-8 concentration increased from 10000pg/ml to about 15000pg/ml slowly in 15 days after operation and then decreased slowly,the last result of concentration is 12000pg/ml. In AAT,CVF, no anti-inflammatory treatment group, the serum IL-8 concentration decreased to about 4000pg/ml then increased to about 10000pg/ml, and decreased again slowly,the last result of concentration is 8000pg/ml.(8)In the4 experimental groups, serum IL-1 concentration was not significantly increased, remained about 7pg/ml after operate.(9)AAT and non inflammatory treatment group, the serum MCP-1 concentration increased from 2200pg/ml to about 5500pg/ml rapidly in 7 days after operation and then decreased to4000pg/ml slowly, CFV and Actemra group, serum MCP-1 concentration increased to about 3000pg/ml slowly.Conclusions:(1)AAT have an anti-inflammatory effect on SIXR,but no single anti-inflammatory agent completely suppressed the inflammatory response, a combination of anti-inflammatory agents may be necessary to achieve long-term pig graft survival in primates.(2)CVF have an anti-inflammatory effect on SIXR, but no single anti-inflammatory agent completely suppressed the inflammatory response.(3)Actemra have an anti-inflammatory effect on SIXR, but no single anti-inflammatory agent completely suppressed the inflammatory response. |
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