Abstract
IntroductionSevere tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system. However, there is little known about the functional alterations of monocytes in the early posttraumatic phase, characterized by the battle of the individual with the initial trauma.MethodsThirteen patients with severe multiple injury; injury severity score (ISS) >16 points (17 to 57) were included. The cytokine synthesis profiles of monocytes were characterized on admission, and followed up 6, 12, 24, 48, and 72 hours after severe multiple injury using flow cytometry. Whole blood was challenged with lipopolysaccharide (LPS) and subsequently analyzed for intracellular monocyte-related TNF-α, IL-1β, IL-6, and IL-8. The degree of organ dysfunction was assessed using the multiple organ dysfunction syndrome (MODS)-score of Marshall on admission, 24 hours and 72 hours after injury.ResultsOur data clearly show that the capacity of circulating monocytes to produce these mediators de novo was significantly diminished very early reaching a nadir 24 hours after severe injury followed by a rapid and nearly complete recovery another 48 hours later compared with admission and controls, respectively. In contrast to the initial injury severity, there was a significant correlation detectable between the clinical signs of multiple organ dysfunction and the ex vivo cytokine response.ConclusionsAs our data derived from very narrow intervals of measurements, they might contribute to a more detailed understanding of the early immune alterations recognized after severe trauma. It can be concluded that indeed as previously postulated an immediate hyperactivation of circulating monocytes is rapidly followed by a substantial paralysis of cell function. Moreover, our findings clearly demonstrate that the restricted capacity of monocytes to produce proinflammatory cytokines after severe injury is not only an in vitro phenomenon but also undistinguishable associated with the onset of organ dysfunction in the clinical scenario.
Highlights
Severe tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system
It can be concluded that as previously postulated an immediate hyperactivation of circulating monocytes is rapidly followed by a substantial paralysis of cell function
Our findings clearly demonstrate that the restricted capacity of monocytes to produce proinflammatory cytokines after severe injury is an in vitro phenomenon and undistinguishable associated with the onset of organ dysfunction in the clinical scenario
Summary
Severe tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system. Circulating blood monocytes express a plethora of mediators, including the major proinflammatory cytokines IL-1β, IL-6, IL-8, and TNFα These cytokines are often considered the engine driving the inflammatory response of the entire organism referred. Any imbalance of the tightly regulated homeostasis of pro- and anti-inflammatory forces causes either a hyperinflammatory or an immunosuppressive state [68] Such dyshomeostasis often results in an uncontrollable cellular dysfunction clinically appearing as multiple organ dysfunction syndrome (MODS) [9,10]. A crucial drawback using of bulk production assays, such as ELISA, for the determination of cytokines in supernatants is the fact that they measure accumulated proteins over the incubation time They become impractical when large numbers of heterogeneous cell populations are to be analyzed ex vivo and restrictively only give global information reflecting the properties of the entire cell population being studied. Intracellular cytokine staining remains unaffected by the short half-life of the proinflammatory mediators or the presence of soluble cytokine inhibitors, such as sIL-1RA and sTNF-Rs, respectively
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