Synergistic effect of polyriboinosinic acid:polyribocytidylic acid and either bacterial peptidoglycans or synthetic N-acetylmuramyl peptides on production of adjuvant-induced arthritis in rats.

Lewis rats developed polyarthritis after a single injection of a water-in-oil emulsion containing various peptidoglycans (PGs) derived from Lactobacillus plantarum. A copolymer of polyriboinosinic acid and polyribocytidylic acid markedly potentiated the arthritogenicity of these PGs. The synthetic adjuvants N-acetylmuramyl-L-alanyl-D-isoglutamine (MurNAc-L-Ala-D-isoGln) and MurNAc-L-Ala-D-Gln were non-arthritogenic, but they did produce severe arthritis when mixed in a water-in-oil emulsion with a copolymer of polyriboinosinic acid and polyribocytidylic acid. Substitution of either L-isoGln or D-isoAsn for the D-isoGln in the MurNAc-L-Ala-D-isoGln markedly reduced its capacity to induce the disease. Taken together with the results of skin testing against various PGs and MurNAc-L-Ala-D-isoGln in the diseased rats, the present results suggest that (i) a minimal essential structure required for development of polyarthritis is related to a larger molecule than either MurNAc-L-Ala-D-isoGln or a monomer of PG, probably to a dimer of PG, and (ii) an antigenic determinant(s) for the delayed-type skin hypersensitivity to PGs exists on a common structure shared among these PGs, possibly somewhere on a monomer of PG not on N-acetylmuramyl peptides.