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B Jeppsson

Publications and source records attributed to B Jeppsson.

At least 19 recordsLinked to original sources

Oxygen radical-dependent expression of CXC chemokines regulate ischemia/reperfusion-induced leukocyte adhesion in the mouse colon.

Activation and accumulation of leukocytes constitute a rate-limiting step in ischemia/reperfusion (I/R)-induced tissue injury. The signalling mechanisms, however, that regulate leukocyte rolling and adhesion in the colonic microcirculation are not known. The objective of the study was to define the role of CXC chemokines (MIP-2 and KC) in I/R-induced leukocyte-endothelial cell interactions in the mouse colon. In C57/B16 mice, colonic ischemia was induced by clamping the superior mesenteric artery for 30 min and leukocyte rolling and stationary adhesion were examined in venules after 120 and 240 min of reperfusion. I/R provoked a clear-cut increase in leukocyte rolling and adhesion in colonic venules. Both MIP-2 and KC were upregulated at the gene and protein level in the reperfused colon. Immunoneutralization of MIP-2 and KC by monoclonal antibodies reduced reperfusion-induced firm adhesion of leukocytes by 73% and 75%, respectively. Interestingly, combined inhibition of MIP-2 and KC additionally decreased leukocyte rolling by 79%, but did not further reduce the number of firmly adherent leukocytes. To study the role of oxygen free radicals (OFRs) in the regulation of CXC chemokine expression, additional animals were pretreated with the xanthine-oxidase inhibitor allopurinol. In fact, allopurinol treatment reduced the colonic levels of MIP-2 and KC by 62% and 64%, respectively. This study elucidates important interactions between OFRs and chemokines in the I/R-induced leukocyte response in the mouse colon. Moreover, our data demonstrate that CXC chemokines play a fundamental role in colonic I/R and that functional interference with CXC chemokines may protect against pathological inflammation in the colon.

Allopurinol↗

Influence of a drink containing different antioxidants and Lactobacillus plantarum 299v on plasma total antioxidant capacity, selenium status and faecal microbial flora.

The aim of the study was to investigate whether a supplement of antioxidants to subjects with a high working pace can influence the antioxidant capacity. The study was parallel and double blind with 98 subjects randomised into two groups. One of the groups was given a test drink with antioxidants for 4 weeks (450 ml/day) while the other group took a corresponding amount of placebo drink. The test drink contained: 2 mg beta-carotene/100 ml, 40 mg alpha-tocopherol/100 ml, 80 mg ascorbic acid/100 ml, 2 mg pyridoxine/100 ml, 15 mg magnesium/100 ml, 0.2 mg manganese/100 ml, 1 mg zinc/100 ml, 0.1 mg copper/100 ml and 10 microg selenium/100 ml. Consumption of the test drink for 4 weeks increased the total plasma antioxidant capacity by 7% (ferric reducing ability of plasma method, P<0.05 compared with the placebo group), and the content of selenium and selenoprotein P in serum was raised by 16-17% (P<0.001 compared with the placebo group). No significant changes were found in the placebo group. The test drink also contained Lactobacillus plantarum 299v (5 x 10(7) cfu/ml) and 4 weeks' consumption led to a significant increase of Lb. plantarum 299v in the faeces. In conclusion, consumption of a drink rich in different antioxidants can increase the antioxidant capacity in subjects with a high working pace. This can be valuable since it may increase the protection against reactive oxygen radicals.

Adult↗

Allopurinol and superoxide dismutase protect against leucocyte-endothelium interactions in a novel model of colonic ischaemia-reperfusion.

BACKGROUND: Leucocyte recruitment is a key feature in ischaemia-reperfusion (I/R)-triggered tissue injury. However, the mechanisms underlying leucocyte-endothelium interactions in the large bowel remain elusive because of a previous lack of models to examine the colonic microcirculation. The aim of this study was to develop and validate a novel method for studying reperfusion-induced leucocyte-endothelium interactions in the colon. METHODS: The superior mesenteric artery was occluded for 30 min in male C57/Bl6 mice and leucocyte responses were analysed in colonic venules after 30-240 min of reperfusion. Analysis of leucocyte rolling and adhesion in colonic venules was made possible by an inverted approach using intravital fluorescence microscopy. RESULTS: Thirty minutes of ischaemia and 120 min of reperfusion induced the strongest and most reproducible increase in leucocyte rolling and adhesion. This was associated with a significant increase in colonic levels of malondialdehyde (MDA). Administration of allopurinol and superoxide dismutase reduced I/R-induced leucocyte responses in a dose-dependent manner. Pretreatment with allopurinol attenuated the tissue content MDA in the colon by more than 60 per cent. CONCLUSION: A new method for examining I/R-induced leucocyte responses in the colonic microcirculation is described. Oxygen free radicals play an important role in triggering leucocyte rolling and adhesion in colonic venules.

Allopurinol↗

Compliance and findings in a Swedish population screened for colorectal cancer with sigmoidoscopy.

AIM: The aim of this study was to evaluate the patterns of compliance and the frequency of adenomas and neoplasms in a Swedish population. METHODS: In 1996, 2000 men and women born in 1935 or 1936 were selected at random from the population registers of Uppsala and Malmö/Lund. All subjects were invited by mail to participate. In a randomised study design, subjects were either called up by a nurse to schedule the appointment for sigmoidoscopy or instructed to call themselves. At sigmoidoscopy subjects with a cancer, an adenoma (neoplastic polyp) or more than three hyperplastic polyps were scheduled for a complete colonoscopy. RESULTS: Thirty-nine percent (770/1988) of all the invited subjects had a sigmoidoscopy. The participation differed between the two centres, 47% at the Uppsala centre and 30% at the Malmö/Lund centre (P<0.01). There was no statistically significant difference between the two different invitation groups. In all, 98 subjects (13%) were planned for colonoscopy. Thirty-one (35%) of the subjects having a colonoscopy were women and 57 (65%) were men. Fifty-five true adenomas were found in 46 subjects. All together, six subjects had proximal adenomas. Five adenocarcinomas were diagnosed, all within the reach of the sigmoidoscope. CONCLUSIONS: The compliance was lower and the adenomas were fewer than expected. To increase compliance it is necessary with rigorously controlled invitation routines.

Adenoma↗

Systemic interleukin-6 response to colorectal surgery originates from the bowel.

BACKGROUND: Surgical trauma evokes a systemic cytokine response which is enhanced in patients with colorectal cancer. The aim of this study was to locate the origin of the systemic cytokine response to colorectal surgery. METHODS: The concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were analysed in systemic and mesenteric venous blood in 12 patients operated on with colorectal resections due to cancer or benign lesions. Immunohistochemical staining and analysis of tissue concentrations of IL-6 and TNF-alpha in homogenates from tumours and benign specimens were performed. RESULTS: Mesenteric venous blood contained higher concentrations of IL-6 compared to systemic venous blood after resection, but not before. Tissue concentration of IL-6 was higher in the tumours compared to the benign specimens and immunohistochemistry revealed an abundance of IL-6 and TNF-alpha in malignant epithelium compared to benign mucosa. CONCLUSION: The higher concentration of IL-6 in venous blood from the mesenterium of the resected colonic segment compared to systemic levels, indicates that the bowel is the source of the IL-6 response to surgical trauma in colorectal surgery.

Aged↗

Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model.

BACKGROUND: The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically. METHODS: Forty-eight male Sprague-Dawley rats were treated daily for 7 days with BB-1101 30 mg/kg or vehicle alone (control) starting 2 days before operation. The breaking strength of standardized left-sided colonic anastomoses was measured on postoperative days 1, 3 and 7. RESULTS: Serum BB-1101 levels were increased at 100 nmol/l in BB-1101-treated rats. The anastomotic breaking strength was 48 per cent higher (P = 0.02) in BB-1101-treated animals compared with controls on postoperative day 3. Neither collagen accumulation nor infiltration of neutrophils in the anastomotic area was influenced by BB-1101 treatment. Net deposition of new collagen in subcutaneous sponges was unaffected by the BB-1101. CONCLUSION: The enhanced breaking strength of colonic anastomoses during the critical early postoperative phase found after administration of a broad-spectrum MMP inhibitor implies that MMPs might increase the risk of anastomotic dehiscence. Presented in part to the third joint meeting of the European Tissue Repair Society and the Wound Healing Society in Bordeaux, France, 24-28 August 1999, and published in abstract form in Wound Repair Regen 1999; 7: A321

Anastomosis, Surgical↗

Administration of Lactobacillus plantarum 299v reduces side-effects of external radiation on colon anastomotic healing in an experimental model.

OBJECTIVE: Preoperative radiotherapy of patients with rectal carcinoma is frequently used to reduce the incidence of local recurrence. However, the radiation therapy is associated with several complications, including diarrhea, retarded anastomotic healing and mucosal atrophy. Exogenous administration of lactobacilli has been demonstrated to be effective in stimulating intestinal mucosal growth and reduce mucosal inflammation. The objective of this study was to examine the effects of Lactobacillus plantarum 299v administration on external radiation injury in colon anastomotic healing at different time points. MATERIAL AND METHODS: Sprague-Dawley rats were treated with Lb. plantarum 299v or saline as control and received external radiation of the lower abdomen (10 Gy/day) on day 3 and 7 of the experiment. After 4 days, a colonic resection with anastomosis was performed. Animals were sacrificed on 4th, 7th and 11th day postoperatively. Body weight, white blood cell (WBC) count, mucosal myeloperoxidase (MPO) activity, hydroxyproline, nucleotide, DNA and RNA content, colonic bacterial microflora, bacterial translocation and histology were evaluated. RESULTS: On the 4th postoperative day body weight, WBC and MPO decreased significantly after radiation. On the 7th postoperative day MPO decreased after radiation. In the two irradiated groups it decreased significantly in the Lb. plantarum group compared to the radiated group without treatment. Collagen concentration on the 7th postoperative day was significantly higher in Lb. plantarum group without radiation compared to the group with radiation without Lb. plantarum. On the 11th postoperative day MPO was significantly higher in irradiated rats without treatment compared to Lb. plantarum treatment. The collagen concentration increased significantly in the irradiated Lb. plantarum group compared to the other two groups. CONCLUSION: The collagen content decreased and MPO activity increased significantly of the colonic anastomosis in irradiated rats without treatment compared to those treated with Lb. plantarum. It therefore seems that administration of Lactobacillus plantarum 299v reduces the intestinal injury and inflammation following external radiation and improves the colonic anastomotic healing.

Journal Article↗

Intestinal permeability in humans is increased after radiation therapy.

PURPOSE: Irradiation inflicts acute injuries to the intestinal mucosa with rapid apoptosis induction and subsequent reduction in epithelial surface area. It may therefore be assumed that the intestinal barrier function is affected. The aim of this study was to compare the mucosal permeability in irradiated rectum and nonirradiated sigmoid colon from patients subjected to radiation therapy before surgical treatment for rectal cancer. METHODS: Segments from sigmoid colon and rectum obtained from irradiated and nonirradiated patients were stripped from the serosa-muscle layer and mounted in Ussing diffusion chambers. The mucosa-to-serosa passage of the marker molecules 14C-mannitol, fluorescein isothiocyanate-dextran 4,400, and ovalbumin was followed for 120 minutes. RESULTS: The permeability to the markers was size-dependent and increased linearly across time in all specimens. The passage of all markers was increased in irradiated rectum compared with nonirradiated sigmoid colon, whereas in specimens from nonirradiated patients there were no differences between rectum and sigmoid colon. Histologic signs of crypt and mucosal atrophy were found in the irradiated rectal specimens. CONCLUSIONS: Early gastrointestinal complications after radiation therapy may be the result of mucosal atrophy in addition to mucosal damage, with a loss of barrier integrity.

Aged↗

Important role of CD18 in TNF-alpha-induced leukocyte adhesion in muscle and skin venules in vivo.

OBJECTIVE: To examine the role of CD 18 in tumor necrosis factor-alpha (TNF-alpha)-induced leukocyte adhesion and extravasation in vivo. MATERIAL: Male wild-type (WT) and mutated mice with hypomorphic expression of CD 18. METHODS: Intravital microscopy was used to quantitate leukocyte-endothelium interactions provoked by TNF-alpha (0.5 microg) in the cremaster muscle and dorsal skin microcirculation. Tissue recruitment of leukocytes was evaluated in wholemounts of the cremaster muscle and in air pouches in the dorsal skin after TNF-alpha stimulation. RESULTS: TNF-alpha markedly increased venular leukocyte adhesion and recruitment in the cremaster muscle and skin in WT. Notably, in CD 18-targeted animals, leukocyte adhesion triggered by TNF-alpha challenge was significantly reduced by 58% and 72% in venules of the cremaster muscle and skin, respectively. Moreover, in CD18-mutants, tissue accumulation of polymorphonuclear leukocytes (PMNLs) provoked by TNF-alpha in the muscle and skin was decreased by 84% and 70%, respectively. Interestingly, the observed level of reduction in TNF-alpha-induced neutrophil adhesion and recruitment in CD18 gene-targeted animals corresponded well with the decrease in CD 18 expression on neutrophils from these mice, i.e. the surface density of CD18 was reduced by 77% in mutants compared to WT. Differential analysis revealed that the extravascular leukocytes comprised more than 90% PMNLs, indicating that neutrophils were the main inflammatory cell responding to TNF-alpha activation. Notably, the expression of CD18 increased by more than two-fold on extravasated neutrophils compared to circulating neutrophils in the peripheral blood both in WT and mutant animals. CONCLUSIONS: These findings suggest that CD18 is a dominant mediator of firm neutrophil adhesion to venular endothelial cells in the muscle and skin stimulated by TNF-alpha in vivo. In addition, this decreased adhesion in CD18-mutants attenuates leukocyte extravasation in response to TNF-alpha activation. Thus, inhibition of CD 18-function may provide an important strategy to inhibit leukocyte recruitment in cytokine-dependent diseases.

Animals↗

Critical role of P-selectin-dependent rolling in tumor necrosis factor-alpha-induced leukocyte adhesion and extravascular recruitment in vivo.

Leukocyte-endothelium interactions are dependent on a coordinated expression and function of specific adhesion molecules. The objective of the present study was to examine the role of selectin function and leukocyte rolling in tumor necrosis factor-alpha (TNF-alpha)-induced leukocyte adhesion and extravasation in venules in vivo. For this purpose, we used intravital microscopy in the mouse cremaster muscle stimulated for 2-3 h with TNF-alpha intrascrotally. Pretreatment with fucoidan, which inhibits P- and L-selectin, and a P-selectin monoclonal antibody (RB40.34) abolished TNF-alpha-stimulated leukocyte rolling. This great reduction in rolling caused a marked attenuation of firm adhesion and extravascular accumulation of leukocytes. When fucoidan and RB40.34 were administrated after stimulation with TNF-alpha, it was found that leukocyte rolling was greatly reduced whereas the number of firmly adherent leukocytes was completely unchanged, suggesting that the inhibitory effect of blocking P-selectin function on firm leukocyte adhesion and recruitment was due to the reduction in leukocyte rolling along the endothelium. Moreover, pretreatment with a monoclonal antibody against intercellular adhesion molecule-1 (ICAM-1) and a platelet-activating factor (PAF)-receptor antagonist had no effect of TNF-alpha-induced leukocyte rolling and adhesion, indicating that molecules other than ICAM-1 and PAF mediate firm adhesion and recruitment of leukocytes in TNF-alpha-activated tissues. Taken together, our data demonstrate that P-selectin function plays an important role in TNF-alpha-induced inflammatory cell recruitment by mediating leukocyte rolling as a precondition for cytokine-provoked firm adhesion and transmigration in vivo. These findings, thus, suggest that inhibition of P-selectin may be a central target for pharmacological intervention in inflammatory diseases.

Adhesiveness↗

Phylogenetic evidence for novel and genetically different intestinal spirochetes resembling Brachyspira aalborgi in the mucosa of the human colon as revealed by 16S rDNA analysis.

Intestinal spirochetes (Brachyspira spp.) are causative agents of intestinal disorders in animals and humans. Phylogenetic analysis of cloned 16S rRNA genes from biopsies of the intestinal mucosa of the colon from two Swedish 60-years old adults without clinical symptoms revealed the presence of intestinal spirochetes. Seventeen clones from two individuals and 11 reference strains were analyzed and the intestinal spirochetes could be divided into two lineages, the Brachyspira aalborgi and the Brachyspira hyodysenteriae lineages. All of the clones grouped in the B. aalborgi lineage. Moreover, the B. aalborgi lineage could be divided into three distinct phylogenetic clusters as confirmed by bootstrap and signature nucleotide analysis. The first cluster comprised 6 clones and the type strain B. aalborgi NCTC 11492T. The cluster 1 showed a 16S rRNA gene similarity of 99.4-99.9%. This cluster also harbored the only other strain of B. aalborgi isolated so far, namely strain W1, which was subjected to phylogenetic analysis in this work. The second cluster harbored 9 clones with a 98.7 to 99.5% range of 16S rDNA similarity to the B. aalborgi cluster 1. Two clones branched distinct and early of the B. aalborgi line forming the third cluster and was found to be 98.7% similar to cluster 1 and 98.3-99.1% to cluster 2. Interestingly, this shows that considerable variation of intestinal spirochetes can be found as constituents of the colonic microbiota in humans, genetically resembling B. aalborgi. The presented data aid significantly to the diagnostic and taxonomic work on these organisms.

Cell Lineage↗

Mucosal in vitro permeability in the intestinal tract of the pig, the rat, and man: species- and region-related differences.

BACKGROUND: The barrier properties of the gastrointestinal mucosa may be studied by measuring its permeability to different-sized marker molecules. Owing to difficulties in obtaining human tissue it is, however, often necessary to extrapolate findings from experimental animals to man. The aim of the present study was to compare regional intestinal mucosal permeability in man, the rat, and the pig, using the same marker molecules and in vitro technique. METHODS: Segments from jejunum, ileum, colon, and rectum were mounted in Ussing diffusion chambers, and the mucosa-to-serosa passage of 14C-mannitol, fluorescein isothiocyanate (FITC)-dextran 4,400, alpha-lactalbumin, ovalbumin, and FITC-dextran 70,000 was studied. RESULTS: Irrespective of species or intestinal region an inverse relationship between the molecular weight of the markers and the permeability was seen. The mannitol permeability was higher in the small intestine than in the colon in man, whereas the rat showed a higher permeability in the ileum than in the jejunum and colon. The FITC-dextran 4,400 permeability was higher in all intestinal regions in the rat than in man and the pig. The macromolecules showed low permeability with no regional differences. CONCLUSIONS: The results showed differences between intestinal regions and between species. Permeability data from the pig correlated fairly well with those of man, whereas the rat differed, making it difficult to extrapolate from the rat to man.

Adult↗

A pharmacokinetic study of 5-FU/leucovorin and alpha-interferon in advanced cancer.

The present study was designed to study 5-FU pharmacokinetics after interferon. Weekly bolus 5-FU (500 mg/m2), immediately followed by leucovorin (60 mg/m2) was given in 14 weekly cycles to 55 gastrointestinal and breast cancer patients. Interferon-alpha was given on days 2, 4 and 6, starting from cycle 2 at a dose of 0.5 million units (MU) and stepwise increased to 12 MU in cycles 12 and 13. Five patients could not tolerate the treatment even at the lowest dose of interferon and 22 patients were unavailable for the pharmacokinetic analysis because of dose reductions of 5-FU. Five patients were able to follow the protocol to 12 MU, whereas most patients were unable to continue owing to toxicity. 5-FU pharmacokinetics was analysed every second cycle. Peak concentration and AUC were increased after 12 MU of interferon, but no other significant influence of interferon on pharmacokinetic parameters of 5-FU was observed.

Adult↗

Influence of glutathione metabolising enzymes in rats with gram-negative sepsis.

OBJECTIVE: To evaluate the role of glutathione metabolising enzymes in rats with Gram-negative sepsis. SETTING: University hospital, Sweden. ANIMALS: 61 male Sprague Dawley rats. INTERVENTIONS: Animals were divided into two groups, one of which was given tert-butyl-4-hydroxyanisole (BHA), a powerful inducer of glutathione metabolising enzymes. A gelatine capsule containing bacteria and adjuvant substances was placed in the abdomen. In one group it contained only adjuvant substances, and the controls underwent sham laparotomy. MAIN OUTCOME MEASURES: Activities of glutathione metabolising enzymes, and histological effect on pulmonary tissue. RESULTS: Activities of glutathione metabolising enzymes were reduced in lung tissue after the induction of sepsis. Pre-treatment with BHA increased enzyme activity and reduced the histological changes. CONCLUSION: Glutathione metabolising enzymes may have a role in sepsis, and pre-treatment with BHA seems to prevent histological changes in pulmonary tissue in septic rats.

Animals↗

Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome.

OBJECTIVE: The influence of the gastrointestinal (GI) microflora in patients with irritable bowel syndrome (IBS) has not been clearly elucidated. This study was undertaken to see if patients with IBS have an imbalance in their normal colonic flora, as some bacterial taxa are more prone to gas production than others. We also wanted to study whether the flora could be altered by exogenous supplementation. In a previous study we have characterized the mucosa-associated lactobacilli in healthy individuals and found some strains with good colonizing ability. Upon colonization, they seemed to reduce gas formation. METHODS: The study comprised 60 patients with IBS and a normal colonoscopy or barium enema. Patients fulfilling the Rome criteria, without a history of malabsorption, and with normal blood tests underwent a sigmoidoscopy with biopsy. They were randomized into two groups, one receiving 400 ml per day of a rose-hip drink containing 5 x 10(7) cfu/ml of Lactobacillus plantarum (DSM 9843) and 0.009 g/ml oat flour, and the other group receiving a plain rose-hip drink, comparable in color, texture, and taste. The administration lasted for 4 wk. The patients recorded their own GI function, starting 2 wk before the study and continuing throughout the study period. Twelve months after the end of the study all patients were asked to complete the same questionnaire regarding their symptomatology as at the start of the study. RESULTS: All patients tolerated the products well. The patients receiving Lb. plantarum had these bacteria on rectal biopsies. There were no major changes of Enterobacteriaceae in either group, before or after the study, but the Enterococci increased in the placebo group and remained unchanged in the test group. Flatulence was rapidly and significantly reduced in the test group compared with the placebo group (number of days with abundant gas production, test group 6.5 before, 3.1 after vs 7.4 before and 5.6 after for the placebo group). Abdominal pain was reduced in both groups. At the 12-month follow-up, patients in the test group maintained a better overall GI function than control patients. There was no difference between the groups regarding bloating. Fifty-nine percent of the test group patients had a continuous intake of fermented products, whereas the corresponding figure for the control patients was 73%. CONCLUSIONS: The results of the study indicate that the administration of Lb. plantarum with known probiotic properties decreased pain and flatulence in patients with IBS. The fiber content of the test solution was minimal and it is unlikely that the fiber content could have had any effect. This type of probiotic therapy warrants further studies in IBS patients.

Abdominal Pain↗

Diverting colostomy increases anastomotic leakage in the rat colon.

In the present study, we examined the effect of a diverting colostomy on the intestinal healing of colonic anastomosis in the rat. For this purpose, we created a colonic stenosis 2 days prior to the formation of a distal one-layer end-to-end anastomosis with or without a proximal double-barreled deviation colostomy in the rats. Radiological examination of anastomotic leakage was performed daily for 4 days and on day 7 after the operation. We found that anastomotic leakage was markedly increased in rats with a diverting colostomy compared to control animals; i.e. the leakage index (percentage of days with leakage during the experimental period) in colostomy rats was 29%, whereas in animals with no colostomy, the leakage index was only 7%. Interestingly, it was observed that anastomosis formation was associated with a higher mortality rate in rats with colostomy diversion (36%) compared to control animals (7%). However, there was no difference in suture holding capacity on day 7. Moreover, body weight decreased significantly in the colostomy group compared to rats without surgical defunctioning when followed for up to 7 days after surgery. Taken together, our novel findings suggest that a diverting colostomy may increase intestinal leakage after anastomosis formation in the rat colon. Thus, the role of proximal colostomy in the protection of colorectal anastomosis needs to be reevaluated and further investigations are required to resolve the influence of surgical defunctioning on intestinal healing.

Anastomosis, Surgical↗

Glucose utilisation in the lungs of septic rats.

Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose ((18)FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of (18)FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. (18)FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions.

Animals↗