Effect of Toll-like receptor 4 deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in a murine model of experimental autoimmune neuritis

Introduction: The aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN).Material and methods: We selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 & mu;g P0 peptide 180-199 emulsion in 25 & mu;l of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 & mu;l of Freund's incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-& gamma; and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit.Results: We found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-& gamma;, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts.Conclusions: Based on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.