Immunostimulatory oligonucleotides in therapy of allergic diseases.

At present, the improvement of hygienic life standards is considered as an environmental condition, increasing the prevalence of allergic diseases, as early contact with some pathogens is, according to the hygiene hypothesis, required for maturation of the immune system. The recognition of microbial components involves acquired and innate immunity mechanisms. Recently, the link between innate and acquired immunity has been discovered. It involves the evolutionarily old Toll-like receptor (TLR) system. Ligands recognised by TLRs include unmethylated deoxycytidil-deoxyguanosine (CpG) motif-containing microbial DNA. TLR-mediated signalling induces expression of cytokines preferentially promoting a Th1-directed response. Therefore, synthetic CpG motif-containing immunostimulatory oligonucleotides could be employed in causal allergy treatment. This review discusses some molecular aspects of the TLR system, as well as results of animal studies and early experiences, including treatment safety, from human clinical trials with immunostimulatory CpG motif-containing oligonucleotides.