Abstract
Propionibacterium acnes (P. acnes) is a gram-positive anaerobic microorganism present in human skin, and has being widely used in clinical trials as a suitable candidate for therapeutic approach to sepsis. A previous study performed by our research group demonstrated that a P. acne killed preparation had an important immunomodulatory role in severe sepsis. Hence, this study we evaluated the immunomodulatory effect of P. acnes preparation on sub-lethal sepsis using a clinically relevant animal model of polymicrobial sepsis. Cecal ligation and puncture (CLP) was performed in male mice under anesthesia. The group pretreated with the P. acnes-killed preparation showed 80% survival at the end of the experiment (10 days) while the sub-lethal group showed 40% survival. There was an increase in the recruitment of leukocytes to the infection site in animals pretreated with the P. acnes-killed preparation, which was confirmed by a histological analysis of the cecum. Reduction in the Tumor Necrosis Factor-alpha (TNF-alpha) level was observed in the group prophylactically treated with the P. acnes-killed preparation compared to the level in the sub-lethal group. However, significant changes were not observed in Interleukin-1β (IL-1) and Interleukin-6 (IL-6) levels between the groups prophylactically treated with P. acnes and those subjected to sub-lethal sepsis. Treatment with the P. acnes-killed preparation also reduced lung injury and reduced the nitric oxide (NO) levels in the peritoneal fluid of the treated animals compared to the levels recorded in the sub-lethal group, a result probably related to the increased recruitment of neutrophils and increased survival. The results obtained suggest that prophylactic treatment P. acnes can mitigate the effects of sepsis, increasing the survival of mice. Key words: Immunomodulation, sepsis, cellular migration, nitric oxide.
Highlights
Sepsis is defined as Systemic Inflammatory Response Syndrome (SIRS) caused by infection, mainly by bacteria and by fungi and virus (Bone et al, 1992; Huttunen and Aittoniemi, 2011)
There was an increase in the recruitment of leukocytes to the infection site in animals pretreated with the P. acnes-killed preparation, which was confirmed by a histological analysis of the cecum
Significant changes were not observed in Interleukin-1β (IL-1) and Interleukin-6 (IL-6) levels between the groups prophylactically treated with P. acnes and those subjected to sub-lethal sepsis
Summary
Sepsis is defined as Systemic Inflammatory Response Syndrome (SIRS) caused by infection, mainly by bacteria and by fungi and virus (Bone et al, 1992; Huttunen and Aittoniemi, 2011). Human sepsis is currently hypothesized to involve an initial proinflammatory burst responsible for hypotension and organ dysfunction, followed by a compensatory anti-inflammatory immune response that leads to an immunosuppressed state, often called immune depression or immune dysfunction (Hotchkiss and Karl, 2003; Riedemann et al, 2003). TNF-α, IL-1 and IL-6 are three cytokines essentially responsible for the features of SIRS and could be potentially useful as biomarkers of sepsis. Beside these markers, interleukin-8 (IL-8), monocyte chemoattractant protein (MCP-1), interleukin-10 (IL-10), C-reactive protein (CRP), procalcitonin (PCT), and lactate can be used as markers in sepsis. No single biomarker of sepsis are ideal, but many are helpful in identifying critically ill patients (Faix, 2013)
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