Therapeutic evaluation of immunomodulators in reducing surgical wound infection.
Therapeutic evaluation of immunomodulators in reducing surgical wound infection.
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DOI：
10.1096/fj.202101019r
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发表时间：
2022-01
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尽管在感染控制实践（包括预防性抗生素）方面取得了许多进展，但手术部位感染（SSI）仍然是全球发病、住院时间延长和死亡的重要原因。我们的先天免疫系统拥有多种强大的抗菌策略，使其在对抗细菌，真菌和病毒感染方面非常有效。然而，病原体使用各种隐形机制来避开先天免疫系统，这反过来又为它们在手术部位的伤口和损伤组织中定植赢得了时间。我们假设免疫调节剂可以在手术部位启动和激活先天免疫反应，可能会减少手术部位的感染。我们使用了三种免疫调节剂; fMLP（甲酰基-蛋氨酸-赖氨酸-脯氨酸）、CCL 3（MIP-1α）和LPS（脂多糖），基于它们引起强烈炎症反应的能力;在铜绿假单胞菌的手术伤口感染模型中评估我们的假设。我们的数据表明，低剂量的这些免疫调节剂的一次性局部治疗显著增加了感染和未感染手术伤口中的促炎反应，并且在减少伤口中铜绿假单胞菌感染方面与强效预防性抗生素（妥布霉素）一样有效（甚至更好）。我们的数据进一步表明，免疫调节剂对组织修复和伤口愈合过程没有不良影响。相反，它们促进了感染和未感染伤口的愈合。总的来说，我们的数据表明，通过免疫调节剂利用先天免疫系统的力量可以显着提高感染控制和潜在的刺激愈合。我们建议，在手术时局部使用这些免疫调节剂，单独或与预防性抗生素联合使用，可能具有对抗SSI的治疗潜力。
Despite many advances in infection control practices, including prophylactic antibiotics, surgical site infections (SSIs) remain a significant cause of morbidity, prolonged hospitalization, and death worldwide. Our innate immune system possesses a multitude of powerful antimicrobial strategies which make it highly effective in combating bacterial, fungal, and viral infections. However, pathogens use various stealth mechanisms to avoid innate immune system, which in turn buy them time to colonize wounds and damage tissues at surgical sites. We hypothesized that immunomodulators that can jumpstart and activate innate immune responses at surgical sites, would likely reduce infection at surgical sites. We used three immunomodulators; fMLP (formyl-Methionine-Lysine-Proline), CCL3 (MIP-1α), and LPS (Lipopolysaccharide), based on their documented ability to elicit strong inflammatory responses; in a surgical wound infection model with Pseudomonas aeruginosa to evaluate our hypothesis. Our data indicate that one-time topical treatment with these immunomodulators at low doses significantly increased proinflammatory responses in infected and uninfected surgical wounds and were as effective, (or even better), than a potent prophylactic antibiotic (Tobramycin) in reducing P. aeruginosa infection in wounds. Our data further show that immunomodulators did not have adverse effects on tissue repair and wound healing processes. Rather, they enhanced healing in both infected and uninfected wounds. Collectively, our data demonstrate that harnessing the power of innate immune system by immunomodulators can significantly boost infection control and potentially stimulate healing. We propose that topical treatment with these immunomodulators at the time of surgery may have therapeutic potential in combating SSI, alone or in combination with prophylactic antibiotics.