While porcine-based biologic meshes are increasingly used for hernia repair, little data exist on tissue responses to such products. Host foreign body reaction, local inflammation, and wound healing are principally controlled by monocytes/macrophages (M/MØs). Exaggerated activation of M/MØs may deleteriously influence mesh integration and remodeling. We hypothesized that common porcine meshes induce the differential activation of M/MØs in vitro.Samples of four acellular porcine-derived meshes, CollaMend (CM; C.R. Bard/Davol), Permacol (PC; TSL/Covidien), Strattice (ST; LifeCell), and Surgisis (SS; Cook Biotech), were exposed to mononuclear cells derived from the peripheral blood of six healthy subjects. Following a 7-day incubation period, supernatants were assayed for interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) using a multiplex bead-based immunoassay system. The four groups were compared using analysis of variance (ANOVA) and Student's t-test.Each mesh type induced differential mononuclear cell activation in vitro. The mean IL-1beta expressions for CM (7,195 pg/ml) and PC (4,215 pg/ml) were significantly higher compared to ST and SS (123 and 998 pg/ml, respectively; P < 0.05). Similar trends were also seen for IL-6 (range 445-70,729 pg/ml), IL-8 (range 11,640-1,045,938 pg/ml), and VEGF (range 686-7,133 pg/ml).For the first time, we demonstrated that porcine meshes induce M/MØ activation in vitro. CM and PC (chemically crosslinked dermis) induced significantly higher cytokine expression compared to ST (non-crosslinked dermis) and SS (small intestine submucosa). These differences are likely related to proprietary processing methods and/or the extent of collagen crosslinking. Further understanding of immunologic effects of porcine-derived biologic meshes will not only allow for a comparison between existing products, but it may also lead to mesh modifications and improvement of their clinical performance.