Rotavirus preferentially replicates in enterocytes and "danger signals" released by these cells are likely to modulate viral immunity. As a model of these events, we studied selected immunomodulators released during rotavirus infection of polarized Caco-2 cells grown in transwell cultures (TW). At early time points post-infection the virus was detected mainly in the apical side of the TWs, but this tendency was progressively lost concomitantly with disruption of the cell monolayer and cell death. Rotavirus-infected cells released IL-8, PGE(2), small quantities of TGF-beta1, and the constitutive and inducible heat shock proteins HSC70 and HSP70, but not IL-1beta, IL-6, IL-10, IL-12p70, or TNF-alpha. This set of immunomodulators is known to induce a non-inflammatory (non-Th-1) immune response, and may be determining, in part, the relatively low T-cell immune response observed in blood samples after RV infection.