The risk of an avian influenza pandemic has put oseltamivir (Tamiflu) in the spotlight and has given rise to rumors that shikimic acid (SK), which is used for the synthesis of Tamiflu, possesses therapeutic activity. This study was undertaken to determine whether SK, either alone or in combination with quercitin (QT) is able to modulate the release of IL-6 and IL-8 from peripheral blood mononuclear cells (PBMCs). The experiments were conducted comparing the properties of SK, both alone and in combination, with those of Tamiflu. The incubation of PBMCs with 100 nM Tamiflu or SK at two concentrations (10 nM; 100 nM) did not produce any change in IL-6 and IL-8 baseline levels (data expressed as incremental change vs. baseline). On the contrary, incubation with SK and QT at both concentrations (10 and 100 nM) produced a significant increase in the release of IL-8 as compared to other groups (4.19 +/- 0.82, SK-QT 10 nM; 3.83 +/- 1.17 SK-QT 100 nM, P < 0.05 vs. baseline 1.00 +/- 0.10, Tamiflu 100 nM 1.35 +/- 0.16, SK 10 nM 1.68 +/- 0.15 and SK 100 nM 1.80 +/- 0.48). The SK-QT combination also proved to be effective in the upregulation of IL-6 (3.08 +/- 0.46, SK-QT 10 nM; 3.60 +/- 0.74 SK-QT 100 nM, P < 0.05 vs. baseline 1.00 +/- 0.26). According to these findings SK alone is not able to modulate innate immunity in antiviral terms. However, the data show that the SK + QT combination, even at low doses, may be effective for the modulation of innate immunity.