title: Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque.
abstract: OBJECTIVE
  We sought to determine the predominant cell type (macrophage, T lymphocyte, B lymphocyte, mast cell) within the area of implantation of the prototypical polypropylene mesh, Gynemesh PS (Ethicon, Somerville, NJ); and to determine the phenotypic profile (M1 proinflammatory, M2 antiinflammatory) of the macrophage response to 3 different polypropylene meshes: Gynemesh PS (Ethicon), and 2 lower-weight, higher-porosity meshes, UltraPro (Ethicon) and Restorelle (Coloplast, Humblebaek, Denmark).
  
  
  METHODS
  Sacrocolpopexy was performed following hysterectomy in rhesus macaques. Sham-operated animals served as controls. At 12 weeks postsurgery, the vagina-mesh complex was excised and the host inflammatory response was evaluated. Hematoxylin and eosin was used to perform routine histomorphologic evaluation. Identification of leukocyte (CD45(+)) subsets was performed by immunolabeling for CD68 (macrophage), CD3 (T lymphocyte), CD20 (B lymphocyte), and CD117 (mast cell). M1 and M2 macrophage subsets were identified using immunolabeling (CD86(+) and CD206(+), respectively), and further evaluation was performed using enzyme-linked immunosorbent assay for 2 M1 (tumor necrosis factor-alpha and interleukin [IL]-12) and 2 M2 (IL-4 and IL-10) cytokines.
  
  
  RESULTS
  Histomorphologic evaluation showed a dense cellular response surrounding each mesh fiber. CD45(+) leukocytes accounted for 21.4 ± 5.4% of total cells within the perimesh area captured in a ×20 field, with macrophages as the predominant leukocyte subset (10.5 ± 3.9% of total cells) followed by T lymphocytes (7.3 ± 1.7%), B lymphocytes (3.0 ± 1.2%), and mast cells (0.2 ± 0.2%). The response was observed to be more diffuse with increasing distance from the fiber surface. Few leukocytes of any type were observed in sham-operated animals. Immunolabeling revealed polarization of the macrophage response toward the M1 phenotype in all mesh groups. However, the ratio of M2:M1 macrophages was increased in the fiber area in UltraPro (P = .033) and Restorelle (P = .016) compared to Gynemesh PS. In addition, a shift toward increased expression of the antiinflammatory cytokine IL-10 was observed in Restorelle as compared to Gynemesh PS (P = .011).
  
  
  CONCLUSIONS
  The host response to mesh consists predominantly of activated, proinflammatory M1 macrophages at 12 weeks postsurgery. However, this response is attenuated with implantation of lighter-weight, higher-porosity mesh. While additional work is required to establish causal relationships, these results suggest a link among the host inflammatory response, mesh textile properties, and clinical outcomes in the repair of pelvic organ prolapse.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Bryan N
authors.initials: BN
authors.lastname: Brown
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Mani
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Alexis L
authors.initials: AL
authors.lastname: Nolfi
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Abramowitch
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA. Electronic address: pmoalli@mail.magee.edu.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Moalli
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D056887:Pelvic Organ Prolapse / Q000378:metabolism / Q000628:therapy*; D011126:Polypropylenes; D013526:Surgical Mesh; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D011126:Polypropylenes
keywords: cytokines; inflammatory response; macrophage phenotype; polypropylene mesh; rhesus macaque