Provided are an inhibitor of activation of an immune response mediated by an HMGB protein, the inhibitor containing at least one compound selected from the group consisting of a phosphorothioate oligonucleotide and a derivative thereof, and a method of screening for an inhibitor or enhancer of activation of an immune response mediated by an HMGB protein, the method including a mixing step of mixing an HMGB protein and a labeled nucleic acid in the presence and absence of a test substance； a quantifying step of quantifying the HMGB protein bound to the labeled nucleic acid； and a determination step of determining that the test substance is an inhibitor of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is less than the amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance and determining that the test substance is an enhancer of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is higher than the amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance.
