MS-associated biallelic combinations of haplogroup J with the alleles CCL5 rs2107538*A, PVT1 rs2114358*G, TNFSF14 rs1077667*C, and IL4 rs2243250*C, which were not associated with MS individually, were identified.
These DCs, which are with strong immunoregulatory characteristics and are functional in down-modulation of MS-like-disease displayed increased production of IL-4, IL-10 and TGF-β and low IL-12.
IL-10, TNF-α, IFN-γ, AOPP, and NOx levels were significantly higher and IL-4 lower in MS patients with a higher 2011 EDSS scores (≥3) as compared with those with EDSS < 3.
We assessed the relationship of stimulated PBMC-produced IFN-γ, TNF-α, IL-4 and IL-10 in modulating relapse risk using a prospective cohort with established relapsing-remitting MS.
The results of this study suggest that intron 3 VNTR polymorphism of the IL-4 gene was positively associated with predisposition to develop MS in Turkish population.
We have previously shown that short-term herpes simplex virus type 1-mediated IL4 gene therapy is able to inhibit experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice and non-human primates.
Additionally neither IL4 nor IL4R genes are susceptibility factors for Brazilian MS but may be able to modify ethnicity-dependent disease risk and penetrance of susceptibility factors.
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.
Our results show that the IL-4 B1 allele is associated with late onset of MS and therefore might represent a modifier of age of onset rather than a susceptibility factor for patients with MS.
Thus, restricted populations of T cells capable of responding to TCGF/IL2/IL4, presumably reflecting in vivo activated cells, are compartmentalized in the nervous system in MS.
Surprisingly, these changes which favour a beneficial, disease-downregulating effect of IL-4 and TGF-beta in MS, were found to be confined to HLA-Dw2-positive patients.