Which pre-hospital triage parameters indicate a need for immediate evaluation and treatment of severely injured patients in the resuscitation area?

PURPOSE: To find ways to reduce the rate of over-triage without drastically increasing the rate of under-triage, we applied a current guideline and identified relevant pre-hospital triage predictors that indicate the need for immediate evaluation and treatment of severely injured patients in the resuscitation area. METHODS: Data for adult trauma patients admitted to our level-1 trauma centre in a one year period were collected. Outpatients were excluded. Correct triage for trauma team activation was identified for patients with an ISS or NISS ≥ 16 or the need for ICU treatment due to trauma sequelae. In this retrospective analysis, patients were assigned to trauma team activation according to the S3 guideline of the German Trauma Society. This assignment was compared to the actual need for activation as defined above. 13 potential predictors were retained. The relevance of the predictors was assessed and 14 models of interest were considered. The performance of these potential triage models to predict the need for trauma team activation was evaluated with leave-one-out cross-validated Brier and logarithmic scores. RESULTS: A total of 1934 inpatients ≥ 16 years were admitted to our trauma department (mean age 48 ± 22 years, 38% female). Sixty-nine per cent (n = 1341) were allocated to the emergency department and 31% (n = 593) were treated in the resuscitation room. The median ISS was 4 (IQR 7) points and the median NISS 4 (IQR 6) points. The mortality rate was 3.5% (n = 67) corresponding to a standardized mortality ratio of 0.73. Under-triage occurred in 1.3% (26/1934) and over-triage in 18% (349/1934). A model with eight predictors was finally selected with under-triage rate of 3.3% (63/1934) and over-triage rate of 10.8% (204/1934). CONCLUSION: The trauma team activation criteria could be reduced to eight predictors without losing its predictive performance. Non-relevant parameters such as EMS provider judgement, endotracheal intubation, suspected paralysis, the presence of burned body surface of > 20% and suspected fractures of two proximal long bones could be excluded for full trauma team activation. The fact that the emergency physicians did a better job in reducing under-triage compared to our final triage model suggests that other variables not present in the S3 guideline may be relevant for prediction.

Change of transfusion and treatment paradigm in major trauma patients.

Trauma promotes trauma-induced coagulopathy, which requires urgent treatment with fixed-ratio transfusions of red blood cells, fresh frozen plasma and platelet concentrates, or goal-directed administration of coagulation factors based on viscoelastic testing. This retrospective observational study compared two time periods before (2005-2007) and after (2012-2014) the implementation of changes in trauma management protocols which included: use of goal-directed coagulation management; admission of patients to designated trauma centres; whole-body computed tomography scanning on admission; damage control surgery; permissive hypotension; restrictive fluid resuscitation; and administration of tranexamic acid. The incidence of massive transfusion (≥ 10 units of red blood cells from emergency department arrival until intensive care unit admission) was compared with the predicted incidence according to the trauma associated severe haemorrhage score. All adult (≥ 16 years) trauma patients primarily admitted to the University Hospital Zürich with an injury severity score ≥ 16 were included. In 2005-2007, the observed and trauma associated severe haemorrhage score that predicted the incidence of massive transfusion were identical, whereas in 2012-2014 the observed incidence was less than half that predicted (3.7% vs. 7.5%). Compared to 2005-2007, the proportion of patients transfused with red blood cells and fresh frozen plasma was significantly lower in 2012-2014 in both the emergency department (43% vs. 17%; 31% vs. 6%, respectively), and after 24 h (53% vs. 27%; 37% vs. 16%, respectively). The use of tranexamic acid and coagulation factor XIII also increased significantly in the 2012-2014 time period. Implementation of a revised trauma management strategy, which included goal-directed coagulation management, was associated with a reduced incidence of massive transfusion and a reduction in the transfusion of red blood cells and fresh frozen plasma.

It is the lateral head tilt, not head rotation, causing an asymmetry of the odontoid-lateral mass interspace.

OBJECTIVE: Asymmetry in odontoid-lateral mass interspace in trauma patients is a common finding that regularly leads to additional diagnostic work-up, since its dignity is not entirely clear. There is little evidence in the literature that atlantoaxial asymmetry is associated with C1-C2 instability or (sub) luxation. Asymmetry in odontoid-lateral mass interspace seems to occur occasionally in healthy individuals and patients suffering a cervical spine injury. Congenital abnormalities in odontoid-lateral mass asymmetry may mimic an atlantoaxial asymmetry. The center of C1-C2 rotation is based in the peg of dens axis; therefore, a C1-C2 rotational influence seems unlikely. So far, no study examined the influence of C0-C1-C2 tilt to an asymmetry in odontoid-lateral mass interspace. SUBJECTS AND METHODS: In order to determine if rotation or tilt influences the lateral atlantodental interval (LADI) and to estimate physiologic values, we examined 300 CT scans of the cervical spine. RESULTS: The mean LADI was 3.57 mm and the mean odontoid-lateral mass asymmetry was 1.0 mm. Head position during CT examination was found to be rotated in 39 % of the cases in more than 5°. Subsequent mean C0/C2 rotation was 4.6°. There was no significant correlation between atlantoaxial asymmetry and head rotation (p = 0.437). The average tilt of C0-C1-C2 was found to be 2°. We found a significant correlation between tilt of C0-C1-C2 and asymmetry in odontoid-lateral mass interspace (p = 0.000). CONCLUSION: We conclude that an atlantoaxial asymmetry revealed in CT scans of the cervical spine occurs occasionally. Since head tilt correlates with an atlantoaxial asymmetry, it is crucial to perform cervical spine CT scans in a precise straight head position.

[Deployment and efficacy of ground versus helicopter emergency service for severely injured patients. Analysis of a nationwide Swiss trauma center]. / Status quo der Boden- und Luftrettung schwerverletzter Patienten. Analyse eines überregionalen Schweizer Traumazentrums.

The influence of the transport mode, i.e. Helicopter Emergency Medical Service (HEMS) versus ground-based Emergency Medical Service (EMS) on the mortality of multiple trauma patients is still controversially discussed in the literature. In this study a total of 333 multiple trauma patients treated over a 1-year period in a level I trauma center in Switzerland were analyzed. Using the newly established revised injury severity classification (RISC) score there was a tendency towards a better outcome for patients transported by HEMS (standardized mortality ratio 1.06 for HEMS versus 1.29 for EMS). Overall a short preclinical time and the presence of an emergency physician (EP) were associated with a better outcome.

Echinomycin in the prevention of heterotopic ossification - an experimental antibiotic agent shows promising results in a murine model.

BACKGROUND: Heterotopic ossification (HO) frequently causes complications following orthopaedic and trauma surgery and may drastically reduce the postoperative outcome due to pain and joint contracture. Current therapeutic options include NSAID's and local radiation. However, both options of prevention show disadvantages such as delayed fracture healing and impaired ossification as well as other side effects.(9) Our goal was to investigate a novel approach in the prevention of heterotopic ossification by pharmacologically interfering with the molecular signalling pathways involved in this process. Hypoxia leads to numerous effects on a cellular level, one of which is the activation of the transcriptional complex hypoxia-inducible factor (HIF).(19) Among several other actions, the HIF1-α signalling pathway in turn regulates angiogenesis through induction of the expression of vascular endothelial growth factor (VEGF).(21) We hypothesised that by pharmacologically interfering with the HIF-1α signalling pathway, the amount of HO formation may be reduced. Echinomycin is a known inhibitor of HIF-1-alpha and was used in our study with the aim to prevent HO from forming. METHODS: We examined the effect of Echinomycin on HO formation in a murine model where an Achilles tenotomy was performed. This has previously been shown to reliably produce islets of heterotopic ossification within the soft tissue of mouse hind limbs at 10 weeks after surgery. The control group underwent Achilles tenotomy only, whereas the Echinomycin group additionally received Echinomycin subcutaneously. After trial completion, the limbs were harvested and Micro-CT was performed. Heterotopic bone volume was then identified in 3d images and quantified. RESULTS: We found a highly significant reduction in the bone volume following subcutaneous administration of Echinomycin compared to the control group. CONCLUSION: Although a substantial reduction could be achieved, it was not possible to completely prevent heterotopic ossification from forming. Further studies have yet to be conducted to optimise the results by altering the dosage and duration of administration as well as investigate the mechanism by which Echinomycin led to the reduction of HO formation.

[Delayed splenic rupture 13 days post-trauma after initially inconspicuous computed tomography examination]. / Zweizeitige Milzruptur am 13. postraumatischen Tag nach initial unauffällig befundener CT-Untersuchung.

Delayed splenic injuries are rare but nevertheless well known and very dangerous complications after blunt abdominal trauma. The highest incidence is reported between four and eight days after trauma; however some cases with a latent period of weeks have been published. We present a case of delayed splenic rupture 13 days after trauma where most computed tomography (CT) examinations were interpreted as normal and present a review of the pathophysiology of delayed rupture, diagnosis and therapy.

[Surgical options of metastatic spine tumors]. / Chirurgische Therapiemöglichkeiten bei Wirbelkörpermetastasen.

Spinal metastases are a common concomitant phenomenon of advanced tumor disease. Beside the lung and liver, the spine is the third most common localization of manifestation. Apart from chronic and increasing pain, spinal metastases lead to neurological deficits due to destruction of the vertebral body and subsequent epidural growth expansion. The aim of a surgical treatment is the reduction of pain and the maintenance of neurological function as well as spine stability. The indication for surgery should be determined individually in an interdisciplinary consultation. The purpose of this article was to provide a brief overview regarding diagnostics and therapy of metastatic spine tumors.

[Minimally invasive balloon-assisted reduction and internal fixation of tibial plateau fractures]. / Minimal-invasive, ballonassistierte Aufrichtung und innere Fixation von Tibiaplateaufrakturen.

The management of tibial plateau fractures can be challenging because of the scarcity of soft tissue associated with a high rate of wound healing disorders. Classic open reduction and internal plate fixation require extensive soft tissue dissection and periosteal stripping, and elevation of depressed fragments and maintenance of the reduction is difficult. In the current report the authors describe a novel operative approach to percutaneously reduce depressed tibial plateau fractures using an inflatable balloon in combination with minimally invasive plate fixation. The results of the first 5 cases treated with this technique are reported.

[Osteoporotic fractures of axial skeleton]. / Osteoporotische Frakturen des Achsenskeletts.

Osteoporotic fractures most frequently first occur in the axial skeleton, especially in the vertebral bodies of the thoracolumbar transition. Beside pain, these fractures cause increasing kyphosis leading to changes in statics and a shift of the bodies' center of gravity. This results in physiological, functional as well as neurological consequences that cannot be managed by means of a conservative therapy. The purpose of this article is to provide a brief overview on diagnostics and therapy of such fractures. Furthermore, fractures of the pubic rami need to be mentioned. They pose another frequent location for osteoporotic fractures and are also associated with a high rate of morbidity and mortality.

Metallic artefact reduction with monoenergetic dual-energy CT: systematic ex vivo evaluation of posterior spinal fusion implants from various vendors and different spine levels.

OBJECTIVES: To evaluate optimal monoenergetic dual-energy computed tomography (DECT) settings for artefact reduction of posterior spinal fusion implants of various vendors and spine levels. METHODS: Posterior spinal fusion implants of five vendors for cervical, thoracic and lumbar spine were examined ex vivo with single-energy (SE) CT (120 kVp) and DECT (140/100 kVp). Extrapolated monoenergetic DECT images at 64, 69, 88, 105 keV and individually adjusted monoenergy for optimised image quality (OPTkeV) were generated. Two independent radiologists assessed quantitative and qualitative image parameters for each device and spine level. RESULTS: Inter-reader agreements of quantitative and qualitative parameters were high (ICC = 0.81-1.00, κ = 0.54-0.77). HU values of spinal fusion implants were significantly different among vendors (P < 0.001), spine levels (P < 0.01) and among SECT, monoenergetic DECT of 64, 69, 88, 105 keV and OPTkeV (P < 0.01). Image quality was significantly (P < 0.001) different between datasets and improved with higher monoenergies of DECT compared with SECT (V = 0.58, P < 0.001). Artefacts decreased significantly (V = 0.51, P < 0.001) at higher monoenergies. OPTkeV values ranged from 123-141 keV. OPTkeV according to vendor and spine level are presented herein. CONCLUSIONS: Monoenergetic DECT provides significantly better image quality and less metallic artefacts from implants than SECT. Use of individual keV values for vendor and spine level is recommended. KEY POINTS: • Artefacts pose problems for CT following posterior spinal fusion implants. • CT images are interpreted better with monoenergetic extrapolation using dual-energy (DE) CT. • DECT extrapolation improves image quality and reduces metallic artefacts over SECT. • There were considerable differences in monoenergy values among vendors and spine levels. • Use of individualised monoenergy values is indicated for different metallic hardware devices.

Low molecular weight heparin-induced skin necrosis-a systematic review.

BACKGROUND: Low molecular weight heparins (LMWHs) are currently used as a standard for anti-thrombotic therapy. Skin necrosis caused by LMWH is a rare and probably under-reported complication. The aim of our systematic review is to analyse the present literature for cases of LMWH-induced skin necrosis, emphasising the pathogenesis, clinical pattern, and management of this rare side effect. METHODS: We performed a Medline literature search (PubMed database) and manual cross-referencing to identify all articles related to LMWH-induced skin necrosis. Data were analysed for type of LMWH used, time until skin necrosis occurred, localisation, size, laboratory findings, switch anticoagulant, complications, and outcome. Additionally, the case of a patient from our hospital is presented. RESULTS: We included a total of 20 articles (21 cases) reporting on LMWH-induced skin necrosis. Skin necrosis occurred locally and distant from the injection site. Heparin-induced antibodies were frequently observed (positive 9/11 articles, negative 2/11). However, severe thrombocytopenia (platelet count <100,000 cells/ml) occurred in only four cases, while platelet count remained normal in 50% of the cases. After patients had been switched to other anti-thrombotic drugs, the clinical course was usually benign; however, reconstructive surgery was necessary in two cases. CONCLUSION: LMWH-induced skin necrosis may occur as part of the heparin-induced thrombocytopenia (HIT) syndrome, but other pathomechanisms, including allergic reactions and local trauma, may also be involved. When HIT is excluded, unfractionated heparin is a safe switch anticoagulant. Otherwise, non-heparin preparations such as hirudin or fondaparinux should be preferred.

Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro.

BACKGROUND: The prolonged administration of heparin for prevention and treatment of venous thromboembolism has been associated with a risk of heparin-induced osteoporosis. Fondaparinux is a new antithrombotic drug that specifically inhibits factor Xa. Because of the known interactions of other antithrombotic agents with bone remodelling, the effects of fondaparinux on human osteoblasts were analysed in vitro. METHODS: Primary human osteoblast cell cultures were incubated with either the low molecular weight heparin dalteparin at concentrations of 30, 300 and 900 microg/ml or with fondaparinux at concentrations of 25, 50, 100, 150, 200 and 250 microg/ml. Cellular proliferation rate and protein synthesis were measured. Expression of genes encoding osteocalcin, collagen type I and alkaline phosphatase was examined by reverse transcriptase-polymerase chain reaction. RESULTS: Incubation with dalteparin led to a significant, dose-dependent inhibition of osteoblast proliferation, inhibition of protein synthesis, and inhibited expression of phenotype markers (osteocalcin and alkaline phosphatase genes) after 3 and 7 days. No inhibitory effects were observed in the fondaparinux-treated cells. CONCLUSION: Fondaparinux did not inhibit osteoblast proliferation in vitro and may reduce the risk of heparin-induced osteoporosis associated with long-term heparin administration.

Granulocyte colony-stimulating factor (G-CSF) reduces not only gram-negative but also gram-positive infection-associated proinflammatory cytokine release by interaction between Kupffer cells and leukocytes.

OBJECTIVE AND DESIGN: An important principle for the beneficial effects of granulocyte colony-stimulating factor (G-CSF), a central mediator in the endogenous host response, is the reduction of systemic cytokine levels in various gram-negative models of sepsis and septic shock. There is debate, however, on whether G-CSF is protective also in gram-positive sepsis and acts directly or indirectly on macrophages and hepatic Kupffer cells (KC). METHODS: KC were harvested from either G-CSF-(200 microg/kg bw i.v.) or saline-pretreated Sprague-Dawley rats and stimulated in vitro for subsequent assessment of cytokine release over 24 h. RESULTS: Pretreatment with G-CSF led to a significant (p<0.05) inhibition of lipopolysaccharide (LPS)-induced release of TNF-alpha (-81%), IL-6 (-82%) and IL-1 beta (-57%). Exposure of KC to heat-killed Staphylococcus aureus (S. aureus/SAC) caused a 2- to 3-fold higher TNF-alpha release, but similar IL-6 levels when compared with those after LPS stimulation. Still, G-CSF proved to significantly reduce the release of both TNF-alpha and IL-6 upon KC exposure with SAC for 24h. Interestingly, in neutropenic animals (100mg/kg cyclophosphamide), G-CSF was not capable to blunt the LPS-induced cytokine release, indicating that the action of G-CSF on KC is not direct in nature but targets cellular communication and function of neutrophils. CONCLUSIONS: The present results demonstrate that pretreatment with G-CSF in vivo effectively prevents the overactivation of KC by both gram-negative and gram-positive bacterial substances, probably via modulation of neutrophil function. Thus, inhibition of proinflammatory cytokine response through G-CSF may represent a promising hepatoprotective approach during systemic inflammation.

Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients.

OBJECTIVE: To compare procalcitonin (PCT) plasma levels of injured patients with the incidence and severity of systemic inflammatory response syndrome (SIRS), infection, and multiple organ dysfunction syndrome (MODS) and to assess the predictive value of PCT for these posttraumatic complications. DESIGN: Retrospective study comparing patients with mechanical trauma in terms of severity of injury, development of infectious complications, and organ dysfunctions. SETTING: Level I trauma center with emergency room, intensive care unit, and research laboratory. PATIENTS: Four hundred five injured patients with an Injury Severity Score of > or =9 points were enrolled in this study from January 1994 to February 1996. INTERVENTIONS: Blood samples were collected on the day of admission and on days 1, 3, 5, 7, 10, 14, and 21 thereafter. MEASUREMENTS AND MAIN RESULTS: We determined PCT serum levels using a specific immunoluminometric assay. We retrospectively evaluated the occurrence of SIRS, sepsis, and MODS using patients' charts. Mechanical trauma led to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (p < .05) and a continuous decrease within 21 days after trauma. Patients who developed SIRS demonstrated a significant (p < .05) increase of peak PCT plasma levels compared with patients without SIRS. The highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9+/-2.5 ng/mL; day 1) or severe MODS (5.7+/-2.2 ng/mL; day 1) with a sustained increase (p < .05) for 14 days compared with patients with an uneventful posttraumatic course (1.1+/-0.2 ng/mL). Moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (p < .0001; logistic regression analysis) severe SIRS, sepsis, and MODS. CONCLUSIONS: These data indicate that PCT represents a sensitive and predictive indicator of sepsis and severe MODS in injured patients. Routine analysis of PCT levels seems to aid early recognition of these posttraumatic complications. Thus, PCT may represent a useful marker to monitor the inflammatory status of injured patients at risk.

Differential effect of anti-TNF-alpha antibody on proinflammatory cytokine release by Kupffer cells following liver ischemia and reperfusion.

To study the role of tumor necrosis factor-alpha (TNF-alpha) for induction of the proinflammatory cytokine cascade after liver ischemia and reperfusion (I/R), rats were injected intraperitoneally with anti-TNF-alpha monoclonal antibodies (mAb) or placebo (IgG1) 30 min prior to global hepatic ischemia. Blood levels of TNF-alpha, interleukin (IL)-1alpha and -6 were determined. In addition, Kupffer cells (KC) were harvested after 60 min of reperfusion and spontaneous cytokine release was measured. Sham-operated animals were used as controls. Levels of proinflammatory cytokines in serum and KC supernatants were detected using specific bioassays and ELISA. Liver I/R resulted in increased (p < .01) serum levels of TNF-alpha, IL-1alpha, and IL-6, which was associated with an enhanced (p < .05) release of these cytokines by KC. In vivo pretreatment with anti-TNF-alpha mAb led to complete neutralization of TNF-alpha serum levels and decreased (p < .01) IL-6 levels (-62%). Moreover, anti-TNF-alpha mAb markedly (p < .05) decreased the release of TNF-alpha (-69%) and IL-6 (-56%) by KC, while IL-1alpha was not affected. These data indicate that TNF-alpha produced early after liver I/R triggers both its own secretion as well as IL-6 release by KC during reperfusion while the release of IL-1alpha occurs independent from TNF-alpha.

Inhibition of caspase activity prevents CD95-mediated hepatic microvascular perfusion failure and restores Kupffer cell clearance capacity.

Using a murine model, we studied the effect of agonistic anti-CD95 antibodies (aCD95) on sinusoidal lining cells and a potential protection by caspase inhibition. C3H/HeN mice were intravenously administered aCD95 (10 microgram/mouse) or unspecific IgG (control) in the presence or absence of the caspase inhibitor z-VAD-fmk. Analysis of hepatic microcirculation using intravital fluorescence microscopy revealed severe (P<0.01) sinusoidal perfusion failure and reduced (P<0.05) phagocytic activity of Kupffer cells (KC) within 2 h. Transmission electron micrographs demonstrated loss of integrity of sinusoidal endothelial cells as early as 1 h after aCD95 application, whereas histological manifestation of hepatocellular apoptosis and hemorrhagic necrosis was most pronounced at 6 h. Blocking of caspase activity attenuated (P<0.01) both hepatic microvascular perfusion failure and KC dysfunction. Accordingly, full protection of the liver from apoptotic damage and intact microarchitecture was observed in histological sections after z-VAD-fmk treatment. Mortality rate was 40% 6 h after aCD95 administration, whereas all animals survived in the z-VAD-fmk group (P<0.05). The activation of caspases through CD95 may primarily lead to damage of sinusoidal endothelial cells and hepatic microvascular perfusion failure. Moreover, reduced phagocytic capacity of KC may contribute to accumulation of toxic metabolites released by dying cells at the local site of inflammation, further aggravating liver injury.

Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair.

OBJECTIVE: To characterize the impact of abdominal aortic aneurysm repair (AAAR) on spontaneous as well as lipopolysaccharide (LPS)-induced gene expression of pro- and anti-inflammatory cytokines. DESIGN: Prospective, controlled in vivo/ex vivo study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Whole blood from 14 consecutive patients undergoing AAAR withdrawn prior to surgery (T1), at the end of ischemia (T2), 90 min after declamping (T3) and on the first postoperative day (T4) was cultured in the absence or presence of LPS. Five patients undergoing elective inguinal hernia repair served as controls. MEASUREMENTS AND RESULTS: While tumor necrosis factor (TNF), Interleukin (IL)-1 and IL-10 plasma concentrations did not increase significantly, IL-6 was elevated at each time point, as compared with T1. Despite the spontaneous release of trace amounts of IL-6, the ability of cultured whole blood to mount a cytokine response in vitro to LPS was impaired for all cytokines studied at T2 (TNF-62%, IL-1-51%, IL-6 -20%, IL-10-51%). The stimulated IL-6 response was restored early after declamping (T3: +56 %) and enhanced 1 day after operation (T4: +144%). In contrast, stimulated TNF and IL-1 responses remained depressed at T3 (TNF -48%, IL-1-64%) and T4 (TNF-40%, IL-1-24%). A biphasic pattern was observed for IL-10 with initial depression at T3 (-51%) and restoration at T4 (+40%). Among the different cytokines monitored, only impaired TNF responsiveness at early reperfusion (T3) correlated with the postoperative course, as reflected by APACHE II. Cytokine response to LPS was maintained or even increased during and after surgery in the whole blood from patients undergoing hernia repair. CONCLUSIONS: Despite consistent development of clinical signs of systemic inflammatory response syndrome (SIRS) and spontaneous release of IL-6 abdominal aortic aneurysm repair produces a state of impaired pro-inflammatory cytokine response upon a subsequent in vitro Gram-negative stimulus. This early impairment of TNF responsiveness seems to correlate with an unfavorable postoperative course.

Differential gene expression of CINC, NOS II, and ICAM-1 in endotoxemic liver cells by rG-CSF.

INTRODUCTION: We have recently demonstrated that recombinant granulocyte colony-stimulating factor (rG-CSF) modulates lipopolysaccharide (LPS)-induced Kupffer cell activation with subsequent reduction in hepatic leukocyte-endothelial cell interaction, thereby achieving protection against microcirculatory perfusion failure and hepatic dysfunction. To further clarify the underlying mechanisms, rG-CSF treated liver cells were tested for the LPS-induced gene expression of cytokine-induced neutrophil chemoattractant (CINC) and intercellular adhesion molecule-1 (ICAM-1) as potential chemotactic and leukocyte-recruiting factors and for the gene expression of inducible nitric oxide synthase (NOS II) as potential modulator of leukocyte adherence. METHODS: Using a collagenase, DNAse/pronase digestion technique, hepatic parenchymal and nonparenchymal cell fractions were obtained from livers of in vivo rG-CSF pretreated Sprague-Dawley rats 2 h after LPS exposure. mRNA transcripts were assessed using northern blot analysis. RESULTS: In control livers only ICAM-1 mRNA was found constitutively expressed in hepatic nonparenchymal cells. rG-CSF per se did not affect NOS II, CINC, or ICAM-1 expression in hepatic liver cells, while LPS induced a marked expression of NOS II, CINC, and ICAM-1 in nonparenchymal cells and, to a lesser extent, in hepatocytes. Administration of rG-CSF prior to LPS exposure tended to increase NOS II, CINC, and ICAM-1 mRNA transcripts in hepatocytes. In nonparenchymal cells, however, NOS II and CINC were found reduced in rG-CSF pretreated animals upon LPS exposure. CONCLUSIONS: The present data show a strikingly different cell type specific pattern of inflammatory response genes in rG-CSF-modulated hepatic endotoxemia. Reduced expression of NOS II, in particular of CINC, in the nonparenchymal cell fraction may contribute to the reduced leukocyte adherence and thus attenuation of cell-dependent tissue injury in rG-CSF pretreated endotoxemic animals.