Repeated Lipoteichoic Acid Injection at Low Concentration Induces Capsular Contracture by Activating Adaptive Immune Response through the IL-6/STAT3 Signaling Pathway

Background:Capsular contracture is the most common complication of breast implantation surgery. Bacterial contamination was considered to play an important role in the occurrence of capsular contracture, and Gram-positive bacteria such as Staphylococcus epidermidis were discovered in the clinical specimens. Lipoteichoic acid (LTA) was a component of the cell wall of Gram-positive bacteria and was sufficient in the pathogenicity of the bacteria. The authors assumed that LTA could trigger the immunologic response against the implant and cause capsular contracture. Methods:The authors developed a rat model of capsular contracture by repeated injection of 10 & mu;g/mL LTA. The histologic changes of the capsule tissue were measured by hematoxylin and eosin, sirius red, Masson, and immunohistochemical staining. The expression of related cytokines was measured by quantitative real-time polymerase chain reaction. The downstream pathway activation was shown by Western blot. The authors also applied tocilizumab, an interleukin (IL)-6 receptor antagonist, to verify the role of IL-6 in this pathologic process. Results:The authors discovered that repeated LTA injection, at a low concentration, could induce the thickening of capsule tissue, the deposition of collagen fiber, and the activation of myofibroblasts. The IL-6/signal transducer and activator of transcription 3 signaling pathway was activated in this process, and the inhibition of IL-6 receptor could relieve the symptoms. B cells and T-helper cells, especially T-helper type 1, could be related to this phenomenon. Conclusions:The authors' research corroborated that subclinical infection could trigger capsular contracture, and the immune system played an important role in this process. The authors' results provided a possible research direction for the mechanism of bacterial infection-induced immune response against breast implants.