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Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Cytokine gene polymorphisms play an important role in SLE. Thus, this study aimed to investigate the associations between interleukin 6 (IL-6) and interleukin 10 (IL-10) promoter single-nucleotide polymorphisms (SNPs) and their susceptibility to SLE and the implications for plasma levels. We genotyped IL-6-174G/C (rs1800795) using mutagenically separated polymerase chain reaction (MS-PCR) and IL-10-1082G/A (rs1800896) and -819C/T (rs1800871) using sequence specific primer polymerase chain reaction (SSP-PCR) in 100 Egyptian patients and 119 controls. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). There was significant increase in the frequency of IL-6 (-174) GG genotype (P < 0.05) and G allele (P < 0.01) compared to controls. A significant increase in the distribution of IL-10 (-1082G/A) GG (P < 0.05) and AA (P < 0.05) genotypes and a significant reduction in the frequency of GA genotype (P < 0.05) was found in SLE patients. The mean serum concentration of IL-6 (P < 0.001) and IL-10 (P < 0.001) was significantly elevated in SLE patients compared to healthy controls. There was no significant association of the most common clinical findings and IL-6 and IL-10 gene polymorphisms in SLE patients. In conclusion, our preliminary study indicated that both GG genotype and G allele of IL-6 (-174G/C) could be considered as risk factors for SLE. In addition, the polymorphisms at IL-10 (-1082 G/G and AA) may play a role in SLE susceptibility in Egyptian patients. Larger prospective studies are needed to confirm our findings., (© The Author(s) 2015.)