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Biomedical subjects

Thomas Hartung

Publications and source records attributed to Thomas Hartung.

At least 91 records · Page 5Linked to original sources
PubMed2003

Heterozygous toll-like receptor 4 polymorphism does not influence lipopolysaccharide-induced cytokine release in human whole blood.

The heterozygous Asp299Gly mutation of the toll-like receptor (TLR) 4, the key receptor for lipopolysaccharide (LPS), has been associated with attenuated inflammatory responses. When 160 healthy volunteers (9% heterozygous and 0.6% homozygous) were genotyped and their LPS-inducible cytokine release was assessed in an ex vivo whole blood test, the responses of heterozygotes did not differ significantly from those of wild-type carriers for any of the cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, interferon-gamma, and granulocyte colony-stimulating factor) or eicosanoids measured or for serum cytokines and C-reactive protein. Ten heterozygous subjects and 12 wild-type control subjects responded similarly to a graded series of LPS and Escherichia coli concentrations, excluding the possibility that allele-specific differences are evident only at low stimulus concentrations or in response to whole pathogens. These data demonstrate that the heterozygous Asp299Gly polymorphism does not exhibit a functional defect in cytokine release after the stimulation of blood monocytes.

Adult↗
PubMed2003

ANP inhibits TNF-alpha-induced endothelial MCP-1 expression--involvement of p38 MAPK and MKP-1.

Atrial natriuretic peptide (ANP) has been shown to reduce tumor necrosis factor-alpha (TNF-alpha)-induced activation of endothelial cells via inhibition of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB pathways. The aim of this study was to determine whether ANP is able to inhibit TNF-alpha-induced expression of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells and to elucidate the mechanisms involved. Pretreatment of human umbilical vein endothelial cells (HUVEC) with ANP significantly reduced TNF-alpha-induced expression of MCP-1 protein and mRNA. The effects of ANP were shown to be mediated via the guanylyl-cyclase (GC)-coupled A receptor. Activation of the other GC-coupled receptor (natriuretic peptide receptor-B) by the C-type natriuretic peptide as well as activation of soluble GC with S-nitroso-L-glutathione (GSNO) exerted similar effects as ANP, supporting a role for cyclic guanosine monophosphate (cGMP) in the signal transduction. Antisense experiments showed a requirement of MAPK phosphatase-1 (MKP-1) induction and therefore, inhibition of p38 MAPK in the ANP-mediated inhibition of TNF-alpha-induced expression of MCP-1. To investigate a potential interplay between TNF-alpha-induced activation of p38 MAPK and NF-kappaB, the p38 MAPK inhibitor SB203580 and a dominant-negative p38 MAPK mutant were used. The results indicated that the blockade of p38 MAPK activity leads to an increased activation of NF-kappaB and therefore, suggest a counter-regulatory action of p38 MAPK and NF-kappaB. As antisense experiments revealed a pivotal role for MKP-1 induction and therefore, p38 MAPK inhibition in ANP-mediated attenuation of MCP-1 expression, this action seems to be rather independent of NF-kappaB inhibition.

Atrial Natriuretic Factor↗
PubMed2003

Febrile temperatures attenuate IL-1 beta release by inhibiting proteolytic processing of the proform and influence Th1/Th2 balance by favoring Th2 cytokines.

We investigated possible feedback mechanisms of febrile temperatures on LPS- and staphylococcal enterotoxin B (SEB)-induced cytokine release in human whole blood. LPS-induced IL-1beta release was inhibited at temperatures >38 degrees C, whereas intracellular proIL-1beta formation as well as the release of other cytokines except IL-18 were only attenuated above 42 degrees C, indicating that febrile temperatures impair the proteolytic processing of proIL-1beta. This attenuated processing is not due to either heat inactivation of caspase-1 or structural changes in proIL-1beta produced at higher temperatures. Instead, we propose that febrile conditions change cytosolic compartmentation or trafficking, so that synthesized proIL-1beta cannot encounter caspase-1. Febrile temperatures also influenced Th1/Th2 cytokine balance. We observed a 3-fold increase in the Th2-cytokines IL-5 and IL-13 and a reduction to 15% of the Th1-cytokine IL-2 when SEB-stimulated whole blood was incubated at 40 degrees C compared with 37 degrees C. These results indicate that fever limits the production of the fever-inducing IL-1beta and also influences the adaptive immune response, favoring Th2 cytokine production.

Antigens, Bacterial↗
PubMed2003

Anti-tumor necrosis factor antibody impairs the therapeutic effect of ceftriaxone in murine pneumococcal pneumonia.

Treatments aimed at inhibition of tumor necrosis factor (TNF) in patients with sepsis have been unsuccessful. Up to 50% of such patients suffer from pneumonia. To determine the effect that treatment with anti-TNF has on pneumococcal pneumonia, mice were intranasally inoculated with Streptococcus pneumoniae and, 25 h later, treated with 1 of the following: (1) control antibody, (2) anti-TNF, (3) ceftriaxone (CEF) with control antibody, or (4) CEF with anti-TNF. In the absence of treatment with CEF, mice displayed high bacterial loads in lungs, and all of these mice died within 5 days after inoculation. Anti-TNF did not influence these outcomes. In contrast, 60% of mice treated with CEF alone survived. Anti-TNF administered together with CEF reduced survival to 40% and was associated with enhanced bacterial outgrowth. These data suggest that treatment with anti-TNF impairs the therapeutic efficacy of CEF during pneumococcal pneumonia.

Animals↗
PubMed2003

Determination of the eicosanoid response to inflammatory stimuli in whole blood and its pharmacological modulation ex vivo.

Recognition of pathogens by immune cells initiates the release of numerous signaling molecules, including cytokines and eicosanoids. Here, we describe a simple procedure by which eicosanoids such as prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)) and thromboxane B(2) (TxB(2)) can be measured using commercial enzyme immunoassays (EIAs) in the supernatant of whole blood stimulated with inflammatory stimuli. This is illustrated for numerous stimuli. The kinetics by which lipopolysaccharide (LPS) induces cyclooxygenase (COX)-2 expression in this setup were determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). The eicosanoid response of the blood of 160 healthy volunteers to 1 microg/ml LPS was measured. To determine whether the action of a drug in vivo is represented ex vivo in the eicosanoid response of blood, one volunteer took a standard dose of a number of commercially available cyclooxygenase inhibitors on different days and the eicosanoid response of his blood to LPS was determined before ingestion as well as 2 and 6 h afterwards. The efficacy of the different pharmaceuticals on cyclooxygenase but not lipoxygenase products or cytokines could be monitored ex vivo. Similarly, ex vivo eicosanoid release was measured in blood from 10 volunteers who had taken 50 mg flurbiprofen. The method described extends approaches for studying whole blood cytokine release to the lipid mediators formed from arachidonic acid. These important signaling molecules represent targets for pharmacological intervention, which can now be monitored in vitro, as well as ex vivo employing the same model. Furthermore, the assay could be used to characterize the immune status of patient groups or to monitor the course of disease.

Adult↗
PubMed2003

High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR.

The recently described family of Toll-like receptors (TLRs) plays a major role in innate immunity by mediating inflammatory reactions against a wide array of pathogens. TLR-2 is reported to interact with various bacterial partial structures including lipoproteins, peptidoglycan, and lipoteichoic acid. Two polymorphisms of the TLR-2 gene have recently been described: Arg753Gln, correlated with the incidence of sepsis in a white population, and Arg677Trp, correlated with the incidence of lepromatous leprosy in an Asian population. Both polymorphisms, when inserted into expression vectors encoding for human TLR-2, reduced stimulation of Chinese hamster ovary cells by synthetic lipopeptides. We furthermore developed a rapid and inexpensive method for the detection of both single nucleotide polymorphisms based on restriction fragment length polymorphism. While no individuals carrying the Arg677Trp SNP were identified in a large group of whites, 9.4% of the study population were found to be heterozygous for the Arg753Gln polymorphism. This ratio is significantly higher than previously reported, and therefore detection of this polymorphism among patients may yield important information for the assessment of risk profiles regarding susceptibility to bacterial infections.

Alleles↗
PubMed2003

Definition of structural prerequisites for lipoteichoic acid-inducible cytokine induction by synthetic derivatives.

The controversy about the immune stimulatory properties of lipoteichoic acid (LTA) from Staphylococcus aureus was solved recently by showing decomposition and inactivation of LTA obtained by conventional purification strategies, as well as pronounced LPS contamination of commercial preparations. By introducing a novel preparation method, the structure of bioactive LTA was elucidated. This structure was confirmed by chemical synthesis. In this work, synthetic LTA derivatives were employed to study the structure-function relationship of cytokine induction in human monocytes. Synthetic LTA induced the same cytokine pattern as highly purified natural LTA. The gentiobiose core could be omitted without affecting bioactivity. The polyglycerophosphate backbone amplified the response to the lipid anchor ( approximately 100-fold) only when substituted with D-alanine, whereas alpha-D-N-acetylglucosamine substituents could be omitted. Replacing D-alanine substituents with L-alanine reduced the activity of the molecule at least 10-fold, indicating stereoselectivity. These results define for the first time the crucial patterns required for the immune recognition of LTA.

Acetylglucosamine↗
PubMed2003

A model of human whole blood lymphokine release for in vitro and ex vivo use.

Endotoxin (lipopolysaccharide, LPS) inducible cytokine release by human whole blood is increasingly used to model inflammatory responses in vitro, to detect the presence of pyrogenic contaminations as well as to monitor disease states or immunomodulatory treatments ex vivo. However, the LPS-stimulated blood model primarily allows the assessment of monocyte responses. Here, a whole blood model was established which allows assessment of lymphocyte responses. Four different superantigens, namely staphylococcal enterotoxin A and B (SEA, SEB), toxic shock syndrome toxin-1 (TSST-1) or streptococcal exotoxin A (SPEA) were tested with respect to the induction of lymphokine release. All superantigens were capable of inducing significant amounts of the lymphokines interferon-gamma (IFNgamma), interleukin 2 (IL-2), IL-4, IL-5, IL-13 and tumor necrosis factor beta (TNFbeta) after 72 h of incubation. Concentration-dependencies and kinetics were determined. Blood from 160 healthy donors was used to assess the variability of SEB-inducible lymphokine release. Interindividual differences were more pronounced compared to LPS-inducible monokine release. However, the individual response was maintained when blood from six donors was tested once a week for 8 weeks, suggesting that the individual response represents a donor characteristic. The model appears to be suitable for the evaluation of immunomodulatory agents in vitro as well as ex vivo.

Bacterial Proteins↗
PubMed2003

Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved.

Lipoteichoic acid (LTA) derived from Streptococcus pneumoniae, purified employing a chloroform/methanol protocol, and from Staphylococcus aureus, prepared by the recently described butanol extraction procedure, was investigated regarding its interaction with lipopolysaccharide (LPS)-binding protein (LBP), CD14, Toll-like receptors (TLRs)-2 and -4, and MD-2. LTA from both organisms induced cytokine synthesis in human mononuclear phagocytes. Activation was LBP- and CD14-dependent, and formation of complexes of LTA with LBP and soluble CD14 as well as catalytic transfer of LTA to CD14 by LBP was verified by PhastGel(TM) native gel electrophoresis. Human embryonic kidney (HEK) 293/CD14 cells and Chinese hamster ovary (CHO) cells were responsive to LTA only after transfection with TLR-2. Additional transfection with MD-2 did not affect stimulation of these cells by LTA. Our data suggest that innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by the clinically most important Gram-positive pathogens. However, the involvement of TLR-4 and MD-2 in this process was ruled out.

Acute-Phase Proteins↗
PubMed2003

Lipopolysaccharide (LPS)-binding protein mediates LPS detoxification by chylomicrons.

Chylomicrons have been shown to protect against endotoxin-induced lethality. LPS-binding protein (LBP) is involved in the inactivation of bacterial toxin by lipoproteins. The current study examined the interaction among LBP, chylomicrons, and bacterial toxin. LBP was demonstrated to associate with chylomicrons and enhance the amount of LPS binding to chylomicrons in a dose-dependent fashion. In addition, LBP accelerated LPS binding to chylomicrons. This LBP-induced interaction of LPS with chylomicrons prevented endotoxin toxicity, as demonstrated by reduced cytokine secretion by PBMC. When postprandial circulating concentrations of chylomicrons were compared with circulating levels of low density lipoprotein, very low density lipoprotein, and high density lipoprotein, chylomicrons exceeded the other lipoproteins in LPS-inactivating capacity. Furthermore, highly purified lipoteichoic acid, an immunostimulatory component of Gram-positive bacteria, was detoxified by incubation with LBP and chylomicrons. In conclusion, our results indicate that LBP associates with chylomicrons and enables chylomicrons to rapidly bind bacterial toxin, thereby preventing cell activation. Besides a role in the detoxification of bacterial toxin present in the circulation, we believe that LBP-chylomicron complexes may be part of a local defense mechanism of the intestine against translocated bacterial toxin.

Acute-Phase Proteins↗
PubMed2003

Cyclic AMP increases endogenous granulocyte colony-stimulating factor formation in monocytes and THP-1 macrophages despite attenuated TNF-alpha formation.

The cytokine granulocyte colony-stimulating factor (G-CSF) is in broad clinical use to treat neutropenia, and trials on its use in immunosuppressed conditions and infections are ongoing. To apply G-CSF effectively, it is crucial to understand the regulation and distribution of its endogenous formation. Since G-CSF release is mediated, at least in part, by TNF-alpha formation, we investigated whether drugs suppressing TNF-alpha also impair G-CSF production. Surprisingly, G-CSF formation was enhanced in lipopolysaccharide (LPS)-stimulated blood from a pentoxifylline-treated patient. In the presence of dibutyryl-cAMP, forskolin, tolafentrine or 3-isobutyl-1-methylxanthine, LPS-induced G-CSF formation was enhanced in THP-1 cells, primary monocytes and whole blood. Correspondingly,rp-8-bromo-cAMP suppressed LPS-induced G-CSF release. Addition of prostaglandin E(2) enhanced and indomethacin suppressed G-CSF formation. Reporter gene studies showed that dibutyryl-cAMP enhanced LPS-induced G-CSF promoter activity, indicating a transcriptional up-regulation. Furthermore, disruption of a newly identified putative cAMP-responsive element (CRE) in the G-CSF promoter demonstrated the regulatory role for G-CSF gene transcription. In conclusion, endogenous G-CSF formation critically depends on both TNF-alpha and cyclooxygenase products, exerting effects via cAMP and the CRE in the G-CSF promoter. This might have bearing for drug side effects, putative G-CSF mimetics and our understanding of G-CSF immunobiology.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-kappaB pathway.

BACKGROUND/AIMS: Phyllanthus amarus is a herbal medicine traditionally applied in the treatment of viral hepatitis. Aim of this study was to investigate potential anti-inflammatory properties of standardized P. amarus extracts concerning a potential influence of P. amarus on endotoxin-induced nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and cytokine production in vivo and in vitro. METHODS: Investigations were performed in rat Kupffer cells (KC), in RAW264.7 macrophages, in human whole blood, and in mice. Cells were stimulated with lipopolysaccharides (LPS) in the presence or absence of P. amarus extracts (hexane, EtOH/H(2)O), mice were treated with galactosamine/LPS as a model for acute toxic hepatitis. Nitrite was measured by Griess assay, prostaglandin E(2) (PGE(2)) by radioimmunoassay, and cytokines by enzyme-linked immunosorbent assay. iNOS and COX-2 were determined by Western blot, activation of NF-kappaB and AP-1 by EMSA. RESULTS: P. amarus EtOH/H(2)O and hexane extracts showed an inhibition of LPS-induced production of NO and PGE(2) in KC and in RAW264.7. The extracts also attenuated the LPS-induced secretion of tumor necrosis factor (TNF-alpha) in RAW264.7 as well as in human whole blood. Both extracts reduced expression of iNOS and COX-2 and inhibited activation of NF-kappaB, but not of AP-1. P. amarus inhibited induction of interleukin (IL)-1beta, IL-10, and interferon-gamma in human whole blood and reduced TNF-alpha production in vivo. CONCLUSIONS: This work shows that standardized extracts of P. amarus inhibit the induction of iNOS, COX-2, and TNF-alpha. Therefore, we report for the first time an anti-inflammatory potential of this traditionally employed herbal medicine both in vitro and in vivo.

Animals↗
PubMed2003

Lipoteichoic acid from Staphylococcus aureus is a potent stimulus for neutrophil recruitment.

Lipoteichoic acid (LTA) is a major immunostimulatory principle of Gram-positive bacteria. Intranasal application of LTA from S. aureus to mice resulted in greatly increased neutrophil and macrophage counts in the bronchoalveolar lavage as well as increased levels of the chemokine KC. The potential of highly pure, bioactive LTA from S. aureus to induce neutrophil recruitment and activation was investigated further in the human system. Although neutrophils expressed the key known receptors, CD14, TLR2 and TLR6, LTA did not induce or prime neutrophils for oxidative burst, or release of chemokines, bactericidal permeability-increasing protein or myeloperoxidase. However, LTA induced a strong release of the chemoattractants LTB4, IL-8, C5a, MCP-1 and the colony-stimulating factor G-CSF in whole blood comparable to stimulation with the same concentration of LPS (S. abortus equi). Further, the cytokine and chemoattractant pattern induced by LTA correlated well with that induced by live S. aureus of the same strain. LTA does not appear to activate neutrophils directly, but is a strong stimulus for the recruitment of phagocytes to the site of infection.

Animals↗
PubMed2003

Lipoteichoic acid is a potent inducer of cytokine production in rat and human Kupffer cells in vitro.

BACKGROUND: Kupffer cells have been proposed to be a major cellular origin of pro-inflammatory mediators in sepsis. However, the cytokine response of Kupffer cells to gram-positive bacteria and their endotoxins peptidoglycan (PepG) and lipoteichoic acid (LTA) has never previously been studied. MATERIALS AND METHODS: Primary cultures of rat and human Kupffer cells were exposed to live Staphylococcus aureus (S. aureus) (4.0 x 10(1) to 4.0 x 10(7) CFU/mL culture medium), as well as highly purified PepG and LTA (0-100 microg/mL). Lipopolysaccharide (LPS) at 1 microg/mL was used for control. In parallel experiments, whole blood obtained from the same rats was stimulated in a similar manner. Accumulation of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in plasma or culture supernatants were assessed by enzyme immuno assays. TNF-alpha and IL-6 mRNA were analyzed by real-time RT-PCR. RESULTS: PepG and LTA, as well as live S. aureus, induced the production of TNF-alpha and IL-6 in Kupffer cells from both species in a time- and dose-dependent manner. Whereas PepG was a more potent inducer of TNF-alpha and IL-6 in whole blood, the opposite seemed to be the case in Kupffer cells. In fact, a 100-fold lower concentration of LTA (1 microg/mL) than of PepG (100 microg/mL) was sufficient to induce a substantial production of both TNF-alpha and IL-6 in the Kupffer cells. TNF-alpha and IL-6 mRNA were induced correspondingly. CONCLUSION: Our results support the contention that gram-positive bacteria may activate cytokine production in Kupffer cells during bacteremia and suggest that LTA is important in this interaction.

Animals↗
PubMed2003

Garlic (Allium sativum L.) modulates cytokine expression in lipopolysaccharide-activated human blood thereby inhibiting NF-kappaB activity.

Garlic is proposed to have immunomodulatory and anti-inflammatory properties. This paper shows that garlic powder extracts (GPE) and single garlic metabolites modulate lipopolysaccharide (LPS)-induced cytokine levels in human whole blood. GPE-altered cytokine levels in human blood sample supernatants reduced nuclear factor (NF)-kappaB activity in human cells exposed to these samples. Pretreatment with GPE (100 mg/L) reduced LPS-induced production of proinflammatory cytokines interleukin (IL)-1beta from 15.7 +/- 5.1 to 6.2 +/- 1.2 micro g/L and tumor necrosis factor (TNF)-alpha from 8.8 +/- 2.4 to 3.9 +/- 0.8 micro g/L, respectively, whereas the expression of the anti-inflammatory cytokine IL-10 was unchanged. The garlic metabolite diallydisulfide (1-100 micro mol/L) also significantly reduced IL-1beta and TNF-alpha. Interestingly, exposure of human embryonic kidney cell line (HEK293) cells to GPE-treated blood sample supernatants (10 or 100 mg/L) reduced NF-kappaB activity compared with cells exposed to untreated blood supernatants as measured by a NF-kappaB-driven luciferase reporter gene assay. Blood samples treated with extract obtained from unfertilized garlic (100 mg/L) reduced NF-kappaB activity by 25%, whereas blood samples treated with sulfur-fertilized garlic extracts (100 mg/L) lowered NF-kappaB activity by 41%. In summary, garlic may indeed promote an anti-inflammatory environment by cytokine modulation in human blood that leads to an overall inhibition of NF-kappaB activity in the surrounding tissue.

Cell Line↗
PubMed2003

Protection with antibody to tumor necrosis factor differs with similarly lethal Escherichia coli versus Staphylococcus aureus pneumonia in rats.

BACKGROUND: Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia. METHODS: Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h. RESULTS: Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P > or = 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6; P = 0.006) and S. aureus (-0.5 +/- 0.04; P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P < or = 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003). CONCLUSION: Antibody to TNF improved host defense and survival rates with both lethal E. coli and S. aureus pneumonia, but protection was greater with E. coli, where TNF concentrations were higher than with S. aureus. The efficacy of antiinflammatory agents in sepsis may be altered by bacteria type.

Administration, Inhalation↗
PubMed2003

How to leverage an endogenous immune defense mechanism: the example of granulocyte colony-stimulating factor.

Our understanding of host defense has exploded during the past two decades. It is temping to take advantage of this knowledge by considering the modulation and control of these mechanisms as therapeutic options. In intensive care medicine, the aim is usually to block an overwhelming inflammatory response, which represents the "bad" side of the double-edged sword of host defense. The obvious danger of such treatment strategies is that impairing the inflammatory reaction means impairing host defense in patients exposed to infectious agents. The alternative approach, i.e., strengthening or supplementing favorable host defense mechanism, has so far been little explored clinically. Granulocyte colony-stimulating factor, the granulocyte colony-stimulating factor, combines the unique properties of an anti-infectious and an anti-inflammatory factor. This attractive profile has led us to various approaches to exploit these immunomodulatory activities. In a recently terminated, placebo-controlled, randomized study, we investigated if prophylactic treatment with rh granulocyte colony-stimulating factor (Filgrastim), at the time a risk can be anticipated such as before an operation, may offer protection from immunoinflammatory dyshomeostasis and thus lower the incidence of postoperative sepsis. Perioperative rh granulocyte colony-stimulating factor administration, compared with placebo treatment, resulted in the prevention of postoperative monocyte deactivation, conservation of an adequate Th1/Th2 ratio, as well as a considerable alleviation of the acute phase response. In parallel, there was a clear tendency toward lowering the rate of postoperative septic complications under the administration of Filgrastim.

Aged↗