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).
Study Design
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).
Conclusion
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.
Key words
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Article info
Publication history
Published online: August 07, 2015
Accepted:
August 2,
2015
Received in revised form:
June 21,
2015
Received:
April 15,
2015
Footnotes
This work was supported by National Institutes of Health awards R01 HD061811 (P.A.M.) and K12HD043441 (B.N.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding source had no involvement in the study design, collection of data, analysis of data, interpretation of data, writing of the report, or the decision to submit for publication.
The authors report no conflict of interest.
Cite this article as: Brown BN, Mani D, Nolfi AL, et al. Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque. Am J Obstet Gynecol 2015;213:668.e1-10.
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© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
