Interleukin 4 is a Th2 cytokine with potent anti-inflammatory properties. Protection from autoimmune encephalomyelitis and multiple sclerosis has been achieved with IL-4 therapy and IL-4 deficient mice developed a more severe form of clinical disease. Four polymorphisms within the IL-4 gene are in strong linkage disequilibrium, including one in the promoter at -590, which controls transcriptional activity. An MS protective role for the heterozygous genotype was confirmed in Spain (exon-1+33 C/T: p=0.003, OR [CI]=0.57 [0.38-0.84]), probably indicative of an MS protection haplotype at 5q31 locus. No difference among MS clinical forms or age at onset was detected.