On the other hand, natural LPS variants or synthetic molecules that inhibit the formation of (TLR4/MD-2/LPS)2 hexamer complex by competing with LPS or other agonists for TLR4/MD-2 and/or CD14 binding are interesting drug candidates targeting diseases that are caused by excessive TLR4 activation by bacterial LPS (sepsis and septic shock) and by endogenous molecules (inflammatory and autoimmune diseases) [36]. Here, TLR4 is linked to autoimmune disease.