The H5N1 and H9N2 avian influenza viruses (AIVs) seriously endanger the poultry industry and threaten human health. Characteristic inflammatory responses caused by H5N1 and H9N2 AIVs in birds and mammals result in unique clinical manifestations. The role of anti-inflammatory regulators, PTX3, Del-1, and GDF-15, in H5N1 and H9N2-AIV-mediated inflammation in birds and mammals has not yet been verified. Here, the expression of PTX3, Del-1, and GDF-15 in DF-1 and MDCK cells infected with H5N1 and H9N2 AIVs and their effect on inflammatory cytokines were analyzed. Infection with both AIVs increased PTX3, Del-1, and GDF-15 expression in DF-1 and MDCK cells. Infection with H9N2 or H5N1 AIV in DF-1 and MDCK cells with overexpression of all three factors, either alone or in combination, inhibited the expression of tested inflammatory cytokines. Furthermore, co-expression of PTX3, Del-1, and GDF-15 enhanced the inhibition, irrespective of the cell line. The findings from this study offer insight into the pathogenic differences between H5N1 and H9N2 AIVs in varied hosts. Moreover, our findings can be used to help screen for host-specific anti-inflammatory agents.