# Inflammation: What's There and What's New?
## 2 Inflammatory Mechanisms
### Amplification of the Inflammatory Response
#### 2.3.1 Immune Response
In more detail, IL-12 released by macrophages and dendritic cells prompts NK cells to release IFN-g. In exchange, macrophage inflammation activities, including the output of further IL-12, are potentiated by NK cell-derived IFN-g. Therefore, during immune responses, the early development of IL-12 and IFN-g potentiates the inflammatory response. Thus, during septic shock, a blockade of IL-12 or IFN-g development or function has been shown to substantially decrease the deleterious inflammatory effects [33]. Several other mediators that are not cytokines also participate in systemic inflammatory response syndrome pathogenesis (SIRS). Platelet-activating factor (PAF) is an autocoid phospholipid released by endothelial cells that regulates cytokine release and amplifies the pro-inflammatory response [34]. The adhesion of neutrophils to endothelial cells seems to be an important factor. PAF's extended involvement in the serum of SIRS patients is associated with a negative outcome. Eicosanoids are metabolites of arachid acid that regulate different processes and reactions during the inflammation response. Leukotrienes (LTC4-LTE4) promote the contraction of endothelial cells, leading to capillary leakage. Thromoxane A2, a catalyst originating from the macrophages and platelets, causes platelet accumulation, as well as vasoconstriction [1]. The response from the immune system is closely regulated and typically acts successfully to decrease inflammation and facilitate tissue recovery. Pro-inflammatory mediators (TNF-a, IL-1, IL-12, and IFN-g) and anti-inflammatory mediators are typically balanced (IL-10, converting growth factor-b and some prostaglandandins). IL-10 is an activated macrophage and dendritic cell inhibitor, and acts as an effective inflammatory response regulator. Following a bacterial endotoxin or intact bacteria challenge, mice that are deficient in IL-10 display hyper-inflammation. Supplementation with exogenous IL-10 increases the anti-inflammatory potential. The first effect of IL-10 is that activated macrophages and dendritic cells inhibit IL-12 development. This causes the subsequent suppression of the development of IFN-g by NK cells and activated T-cells, allowing the pro-inflammatory response to inhibit IL-12/IFN-g-mediated amplification [35]. Granulocyte colony-stimulating factor is another cytokine with anti-inflammatory effects (G-CSF). For improved killing operations, G-CSF induces neutrophil production from bone marrow and primes neutrophils. At the same time, by communicating with G-CSF receptors on monocytes and macrophages, G-CSF inhibits the development of TNF-a, IL-1, and IL-12. In addition, the contents of IL-1 ra and TNF receptors are increased by G-CSF therapy. G-CSF thus facilitates local anti-microbial defense by improving the roles of neutrophils while systemically exerting anti-inflammatory effects [36]. Extreme systemic inflammation, namely sepsis and SIRS, can ensue in cases where the pro-inflammatory response predominates. In comparison, the predominance of the anti-inflammatory response can contribute to the creation of a state of relative immunosuppression. This condition also occurs in the post-septic state following major trauma or thermal damage and has been dubbed counter-anti-inflammatory reaction syndrome (CARS). A high number of scientific reports state that the predominance of IL-10 contributes to post-inflammatory immunosuppression growth. CARS-exhibiting patients may be more vulnerable to contagious complications. As a consequence of extreme inflammation, if the pro- and anti-inflammatory paths are out of control, organs can start to fail and a patient can die [37].