Abstract
Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional formula that has long been used for treatment of inflammatory diseases in Traditional Chinese Medicine. In this study, we examined its protective effect against sepsis in an experimental septic model induced by cecal ligation and puncture (CLP) in rats. The results demonstrated that prophylactic administration of HLJDT protected rats from CLP-induced lethality and ameliorated CLP-induced liver and lung injury. HLJDT treatment suppressed the production of proinflammatory cytokines, including TNF-α, IL-1, IL-6, and IL-17A, indicating HLJDT could limit excessive inflammatory responses in septic condition. In addition, HLJDT facilitated bacterial clearance by increasing phagocytic activities of peritoneal macrophages. Furthermore, HLJDT treatment reversed CLP-induced suppression of IFN-γ expression and blocked CLP-induced increase in IL-4 expression in spleens of rats at 24 h after CLP, indicating that HLJDT could reverse the shift from Th1 to Th2 response and promote Th1/Th2 balance toward Th1 predominance in septic rats. Moreover, HLJDT also inhibited the expression of IL-17A and ROR-γt in spleens of septic rats, indicating HLJDT is able to inhibit Th17 activation in septic condition. In conclusion, the present study demonstrated the protective effects of HLJDT against sepsis and highlighted the potential of HLJDT as a medication for septic patients.
Highlights
Sepsis is the systemic response of the host towards invading microorganisms and their toxins [1, 2]
In order to evaluate protective effect of HLJDT against sepsis, rats were treated with different doses of HLJDT (120 and 270 mg/kg) 2 h before cecal ligation and puncture (CLP)
Further determining the cytokine mRNA levels in liver, lung, and kidney by qRT-PCR revealed that CLP significantly enhanced the gene expression of these cytokines at 24 h after surgery, and treatment with 270 mg/kg of HLJDT resulted in a significant suppression of the expression of proinflammatory cytokines, including TNF-α, IL-1, IL-6, and IL-17A within these organs of septic rats, whereas the enhanced expression of anti-inflammatory cytokine IL-10 was not significantly affected (Figure 2(b)). These results suggested that HLJDT can selectively suppress the expression of proinflammatory cytokines, reduce the release of these inflammatory mediators into blood circulation, and attenuate the systemic inflammatory responses in septic rats
Summary
Sepsis is the systemic response of the host towards invading microorganisms and their toxins [1, 2]. The early hallmark sign of sepsis is a whole-body inflammatory state called systemic inflammatory response syndrome (SIRS). This early phase of excessive systemic inflammation can compromise the function of distinct organ systems, leading to multiple organ dysfunction syndrome (MODS) [1, 4]. TNF-α and IL-1 are the most important proinflammatory cytokines, they act synergistically in activating target cells and inducing the production of more inflammatory mediators and are largely responsible for the clinical manifestations of sepsis [6, 8]. The initial excessive inflammatory response is progressively counterbalanced by the negative feedback of anti-inflammatory process, which may adversely affect immune functions leading to inability to Evidence-Based Complementary and Alternative Medicine clear the infection and predisposition to secondary nosocomial infections thereby having a deleterious effect on patient outcome [13, 14]
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