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Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy.

Khanna A, Plummer M, Bromberek K, Woodliff J, Hariharan S - Med Immunol (2002)

Bottom Line: Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute).RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone.Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine (Nephrology), Medical College of Wisconsin, Milwaukee WI-53226, USA. akkhanna@mcw.edu

ABSTRACT
BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL. Blood was drawn on day zero and 14 days post treatment. Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute). The mRNA expression was studied by RT-PCR and serum levels of cytokines were quantified by ELISA and a cytokine bead array system. RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone. The mRNA expression of proinflammatory cytokines TNF-alpha (p < 0.05), cyclins G (p < 0.01) and E (p < 05) were decreased, and of TGF-beta (p < 0.03) and p21 (p < 0.05) were increased in patients treated with this combination. Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination. CONCLUSION: These novel findings demonstrate that addition of SRL to TAC therapy enhances immuno modulation and causes increased immunosuppression providing a rationale for this concomitant therapy.

No MeSH data available.


Related in: MedlinePlus

IL-6, IL-10 and TNF-α mRNA expression: The ratios of IL-6, IL-10 and TNF-α with housekeeping gene β-actin with TAC/MMF/Aza (day #0) and TAC and SRL (day # 14) are shown in the figure.
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Figure 4: IL-6, IL-10 and TNF-α mRNA expression: The ratios of IL-6, IL-10 and TNF-α with housekeeping gene β-actin with TAC/MMF/Aza (day #0) and TAC and SRL (day # 14) are shown in the figure.

Mentions: Figure 4 illustrates comparison of the IL-6 and IL-10 mRNA expression in patients treated with TAC/MMF/Aza and TAC/SRL. The results are expressed as ratio with β-actin, a significant (p < 0.01) increase in IL-10 mRNA in patients treated with both TAC and SRL (0.84 ± 0.1), when compared with TAC and MMF/Aza (0.47 ± 0.1). Though an increase in IL-6 mRNA was observed in renal transplant recipients treated with TAC/SRL (0.72 ± 0.2) compared to patients treated with TAC/MMF/Aza (0.59 ± 0.16), the difference was not significant.


Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy.

Khanna A, Plummer M, Bromberek K, Woodliff J, Hariharan S - Med Immunol (2002)

IL-6, IL-10 and TNF-α mRNA expression: The ratios of IL-6, IL-10 and TNF-α with housekeeping gene β-actin with TAC/MMF/Aza (day #0) and TAC and SRL (day # 14) are shown in the figure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC149406&req=5

Figure 4: IL-6, IL-10 and TNF-α mRNA expression: The ratios of IL-6, IL-10 and TNF-α with housekeeping gene β-actin with TAC/MMF/Aza (day #0) and TAC and SRL (day # 14) are shown in the figure.
Mentions: Figure 4 illustrates comparison of the IL-6 and IL-10 mRNA expression in patients treated with TAC/MMF/Aza and TAC/SRL. The results are expressed as ratio with β-actin, a significant (p < 0.01) increase in IL-10 mRNA in patients treated with both TAC and SRL (0.84 ± 0.1), when compared with TAC and MMF/Aza (0.47 ± 0.1). Though an increase in IL-6 mRNA was observed in renal transplant recipients treated with TAC/SRL (0.72 ± 0.2) compared to patients treated with TAC/MMF/Aza (0.59 ± 0.16), the difference was not significant.

Bottom Line: Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute).RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone.Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine (Nephrology), Medical College of Wisconsin, Milwaukee WI-53226, USA. akkhanna@mcw.edu

ABSTRACT
BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL. Blood was drawn on day zero and 14 days post treatment. Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute). The mRNA expression was studied by RT-PCR and serum levels of cytokines were quantified by ELISA and a cytokine bead array system. RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone. The mRNA expression of proinflammatory cytokines TNF-alpha (p < 0.05), cyclins G (p < 0.01) and E (p < 05) were decreased, and of TGF-beta (p < 0.03) and p21 (p < 0.05) were increased in patients treated with this combination. Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination. CONCLUSION: These novel findings demonstrate that addition of SRL to TAC therapy enhances immuno modulation and causes increased immunosuppression providing a rationale for this concomitant therapy.

No MeSH data available.


Related in: MedlinePlus