Romanian Society of Pharmaceutical Sciences

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EFFECT OF INTERLEUKIN-6 POLYMORPHISM ON FUNCTION OF THE RENAL ALLOGRAFT FUNTION AND EFFICACY OF IMMUNOSUPPRESSIVE THERAPY

MACIEJ KOTOWSKI 1,2*, ANNA BOGACZ 3,4, JOANNA BARTKOWIAK-WIECZOREK 5, JERZY SIENKO 2, KAROL TEJCHMAN 2, KRZYSZTOF DZIEWANOWSKI 6, MAREK OSTROWSKI 2, BOGUSŁAW CZERNY 3,8, EDMUND GRZEŚKOWIAK 5, BOGUSŁAW MACHALIŃSKI 1

1.Department of General Pathology, Pomeranian Medical University, Szczecin, Poland
2.Department of General Surgery and Transplantation, Pomeranian Medical University, Szczecin, Poland
3.Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland
4.Department of Histocompatibility with Laboratory of Genetic Diagnostics, Regional Blood Centre, Poznan, Poland
5.Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, University of Medical Sciences, Poznan, Poland
6.Nephrology-Transplant Centre, Department of the Regional Public Hospital in Szczecin, Szczecin, Poland
7.Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, Szczecin, Poland

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The administration of immunosuppressive drugs affects the improvement of organ transplants. However, they can have a double effect, because it is well established that immunosuppressive drugs may result in nephrotoxicity related to the development of chronic graft dysfunction and acute rejection. The aim of the study was to determine a correlation between the therapeutic effect of immunosuppressants and IL-6 -174G > C polymorphism in patients after renal transplantation. A total of 185 patients receiving cyclosporine (CsA) were involved. The genotype frequencies were determined using the real-time polimerase chain reaction (PCR) method. The highest doses of cyclosporine were used for carriers of the GG genotype (GG: 196.00 mg vs GC: 169.70 mg and CC: 170.00 mg, p = 0.77). No such correlations were found for the determined blood concentration of CsA, because carriers of the CC genotype had slightly lower mean drug concentration in the blood as compared to the individuals with the GG and GC genotypes (CC: 112.41 ± 6.95 ng/mL vs GG: 119.08 ± 51.31 ng/mL and GC: 135.24 ± 28.68 ng/mL, p = 0.78). In addition, a comparison of the IL-6 genetic variants and the biochemical parameters found no potential risk for transplant rejection. However, the results obtained for creatinine suggest that patients with the CC genotype and receiving CsA may be at high risk of kidney graft rejection. These results indicate that IL-6 polymorphism may influence the dosage of immunosuppressive drugs in patients after transplantation as far as the individualization of therapy is concerned.