Figure 2. Effect of immunosuppressive therapy (IS) on pro-inflammatory cytokines, chemokines and C-RP levels in relation to activation of coagulation in pig artery patch recipients.
(A) Blood cytokine and chemokine levels after pig artery patch transplantation in comparison to naïve baboons at 14 and 28 days after transplantation. With no IS, elevated levels of IL-12, IFNγ, TNFα, MCP-1 and IL-8 were observed, and was markedly reduced with IS (n=5), whereas IL-6 levels were elevated with IS in comparison to naïve baboons and when no IS was given.
(B) Platelet counts, D-dimers and fibrinogen were evaluated in pig artery patch recipients at 2 weeks and one month after transplantation in comparison to naïve baboons. In naïve baboons, platelet numbers were 250+/−52×103/mm3, D-dimer levels were 1.3+/−1.1μg/mL, and fibrinogen levels were 166+/−43mg/dL. In pig artery patch recipients, platelet numbers were significantly elevated at 2 weeks without IS (395+/−109×103/mm3) or with IS (406+/−107×103/mm3), and at 4 weeks without IS (446+/−159×103/mm3) or with IS (484+/−107×103/mm3) (p<0.001). Without IS, fibrinogen levels remained comparable to those in naïve baboons at 2 weeks (149+/−36mg/dL) and at 4 weeks (161+/−28mg/dL). With IS, fibrinogen levels were slightly elevated at 2 weeks (216+/−98mg/dL), and elevated significantly at 4 weeks (354+/−72mg/dL) (p<0.001). D-dimer levels were significantly elevated at 2 weeks without (1.7+/−0.6μg/mL) or with (1.5+/−0.6μg/mL) IS, and at 4 weeks without IS (3.3+/−1.2μg/mL) or with IS (3.5+/−1μg/mL IS (p<0.001).
(C) Immunosuppression reduced TAT levels in pig artery patch recipients (left). In naïve baboons, TAT levels were 16.3+/−10μg/L. TAT levels were elevated after transplantation with no IS (235.3+/−144.4μg/L), but were reduced to normal levels when IS had been administered (14.2+/−7μg/L). There was a significant positive correlation (r2=0.7956; p<0.01) between TAT levels and absolute CD3+T cell numbers in pig artery patch recipients (right).
(D) C-RP levels in blood were measured before and after pig artery patch xenotransplantation and the fold increase in C-RP levels was determined. Without IS, there was no increase in C-RP level, whereas with IS there was a significant increase. There was a significant negative correlation between C-RP levels and the number of CD3+T cells, and a significant positive correlation between C-RP levels and IL-6 and fibrinogen levels.