The Effect of Atorvastatin (Lipitor) on the Duration of Survival of Allogeneic Skin Graft and the Growth of B16F10 Melanoma Cells in Mice
Nabil Zeidan
Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, Lebanon.
Fadi El-Rami
Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, Lebanon.
Nayla S. Al-Akl
Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, Lebanon.
Alexander M. Abdelnoor *
Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, Lebanon.
*Author to whom correspondence should be addressed.
Abstract
Aims: To evaluate the immunomodulatory effect of using non-cholesterol lowering dose of atorvastatin (AS) on skin allograft survival and on tumor growth in mice.
Study Design: Experimental Study.
Place and Duration of Study: Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut; 2011-2012.
Methodology: BALB/c mice were transplanted with skin allografts from C57BL/6 mice and given either AS alone or in combination with immunosuppressive agents. Average survival days of skin allografts were recorded and serum levels of interleukin-1β (IL-1β) and interferon-γ (IFN-γ) were quantified. BALB/c mice and C57BL/6 mice were challenged intraperitoneally with B16F10 melanoma cancer cells (cancer cell line syngeneic to C57BL/6 mice) and were then treated with AS. They were observed regularly for tumor growth.
Results: The results indicated that in transplant mice AS given alone or in combination with immunosuppressive agents prolonged allograft survival time through non-cholesterol lowering mechanisms in spite of a non-significant change in serum cytokine levels. Furthermore, AS treatment enhanced tumor growth in C57BL/6 mice and promoted tumor growth in BALB/C mice.
Conclusion: It can be speculated that AS down expresses TLR and modifies MHC presentation resulting in hindering the generation of an innate and adaptive immune response.
Keywords: Immunosuppression, skin transplantation, cancer, statins, cytokines