ABSTRACT
Aim: The aim of this study was to examine whether a Human herpes virus-6 (HHV-6) infection increases the risk of MS in individuals harboring particular cytokine receptor α- chain gene alleles. Study Design: MS patients and controls were assessed for HHV-6 DNA and for single nucleotide polymorphisms (SNPs) in their IL7RA and IL2RA genes. Place and Duration of Study: The study was carried out at the Department of Experimental Pathology, Microbiology and Immunology, American University of Beirut, between March 2011 and March 2013. Methodology: Blood samples from 100 MS patients and 100 controls were investigated for the presence of HHV-6 by nested PCR. Single nucleotide polymorphisms (SNPs) in the IL7RA and IL2RA genes were examined by restriction fragment length polymorphism. Results: HHV-6 was detected in 58% of MS patients and 32% of controls (OR = 2.935, 95% CI = 1.582-5.463, p=0.000). We did not detect a statistically significant correlation between MS and the studied rs2104286, rs12722489 SNPs in the IL2RA gene and rs6897932 SNP in the IL7RA gene. Concomitant presence of rs2104286 and HHV-6 was detected in 56% of patients and 30% of controls (OR=2.970, 95% CI=1.594-5.53, P=0.000). Similarly, rs6897932 and HHV-6 were observed in 57% of patients and 28% of controls (OR=3.409, 95% CI= 1.815-6.428, P=0.000). Therefore, double positivity moderately increased the risk of MS compared to either factor alone. HHV-6 and rs12722489 double positivity did not increase the risk of MS. Conclusion: HHV-6 infections may enhance the risk of MS in subjects with particular genetic determinants.
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 noncholesterol 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.