How LPS may affect these issues in digestion.

Weight loss
Breakage and depletion of microvilli
The tight junctions widen and become disrupted.
Gut inflamation
Leaky Gut
Digestive symptoms
Disrupted Intestinal Transit
LPS is linked to the problems of gluten,soy and dairy in ASD children

LPS and Weight Loss

View this article in PubMed
1: Cytokine. 1993 Jul;5(4):285-90.
The role of interleukin-6 in lipopolysaccharide-induced weight loss, hypoglycemia and fibrinogen production, in vivo.

* Strassmann G, * Fong M, * Windsor S, * Neta R.

Department of Immunology, Otuska America Pharmaceutical, Inc., Rockville, MD 20850.

It was recently shown that interleukin (IL)-6 is an important mediator involved in the Colon (C)-26 model of experimental cancer cachexia. In this study, we wished to determine whether IL-6 is also involved in several metabolic changes associated with lipopolysaccharide (LPS) challenge.

Administration of a relatively high amount of LPS to mice induced a transient weight loss, hypoglycemia, hypertriglyceridemia and an increase in the hepatic acute phase reactant, fibrinogen. Pretreatment of mice with the rat anti-murine IL-6 antibody (20F3), but not with a control antibody, resulted in a significant improvement of LPS-induced hypoglycemia and weight loss as well as a significant decrease of plasma fibrinogen. Anti-IL-6 antibody had no effect on LPS-induced hypertriglyceridemia. On the other hand, the pretreatment of mice with anti-murine TNF (TN3.19) antibody was able to completely inhibit elevation of triglycerides and modestly improve LPS-induced weight loss although it had no effect on hypoglycemia and fibrinogen production. Taken together, these results suggest that IL-6 plays a role in some of the metabolic changes associated with both an acute (i.e. LPS challenge) and chronic (C-26 cachexia) inflammatory conditions.

PMID: 8260592 [PubMed - indexed for MEDLINE]

LPS causes intestinal injuries

The next article shows that LPS causes the tight junctions to widen and become disrupted. Please note that this alteration plays an important role in creating a leaky gut. The other changes induced by LPS are also critical, broken microvilli are a sign of celiac disease.

View this article in PubMed
1: Zhongguo Dang Dai Er Ke Za Zhi. 2006 Oct;8(5):425-8. Links
[Protective effects of recombinant intestinal trefoil factor against intestinal injuries induced by endotoxin in young rats]
[Article in Chinese]

* Li J, * Xu LF, * Sun M, * Li Q, * Gao H, * Jiang WG.

Department of Pediatrics, Second Affiliated Hospital of China Medical University, Shenyang 110004, China. lijun9524@126.com

OBJECTIVE: This study aimed to investigate the protective effects of recombinant intestinal trefoil factor (rITF) against intestinal injuries and the possible mechanism by examining the changes of diamine oxidase (DAO) and TNF-alpha and the intestinal ultrastructural changes in lipopolysaccharide (LPS) induced intestinal injuries. METHODS: Ninety-six ten-day-old Wistar rats were randomly injected with either normal saline (1 mL/kg, Control group), LPS (1 mL/kg) or LPS (1 mL/kg) + rITF (0.1 mL) intraperioneally. At 2, 6, 24 and 72 hrs after administration plasma DAO activity was determined using absorption spectrometry; and the intestinal protein and mRNA expression of TNF-alpha were measured using immunohistochemistry and RT-PCR methods. The intestinal ultrastructural changes were observed by electron microscopy. RESULTS: The plasma DAO activity in the LPS group began to increase at 2 hrs, peaked at 6 hrs and remained at significantly higher levels until 72 hrs after administration compared with the Control group (P < 0.01). The plasma DAO activity in the LPS + rITF group decreased noticeably compared with the LPS group at all time points (P < 0.01 or 0.05). A significant difference in the plasma DAO activity was only observed at 6 hrs after administration between the LPS + rITF and the Control group. The expression of TNF-alpha protein in the LPS group significantly increased at each time point, peaking at 6 hrs after LPS administration, with the IODT of TNF-alpha of 37,247.64 +/- 3,387.59 vs 6,191.02 +/- 482.32 (P < 0.01) compared with the Control group. rITF treatment decreased the expression of TNF-alpha protein although it remained significantly higher than in the Control group (P < 0.01). The TNF-alpha mRNA was weakly expressed in the Control group but strikingly increased after LPS injection (P < 0.01). Compared with the LPS group, the TNF-alpha mRNA expression in the LPS + rITF group decreased at all time points (P < 0.01 or 0.05). Vacuole changes of mitochodrium, cell nucleus condense, break and depletion of part of microvilli, and widen and disrupted tight junction were observed in the LPS group. The ultrastructural changes of intestinal tissues were improved in the LPS + rITF group. CONCLUSIONS: rITF can decrease the plasma DAO activity and inhibit the expression of TNF-alpha, resulting in a protective effect against intestinal injuries induced by LPS in young rats.

PMID: 17052407 [PubMed - indexed for MEDLINE]

LPS plays a major role in IBD

View this article in PubMed
1: Res Exp Med (Berl). 1986;186(1):61-9.
Lipopolysaccharide-induced colitis in rabbits.

* Hotta T, * Yoshida N, * Yoshikawa T, * Sugino S, * Kondo M.

An experimental animal model of human ulcerative colitis using lipopolysaccharide (LPS) was studied. Rabbits were skin-sensitized by LPS and challenged with intrarectal instillation of LPS after 1% formalin enema. The course of experimental colitis was followed by performing serial colonofiberscopic examinations and biopsy. Petechiae appeared from the 8th hour, and ulcers and bleeding on the 3rd day. Mild macroscopic changes continued for about 2 weeks. By repeating the LPS enema after the initial treatment, the colitis was maintained for over 1 month. Control groups without formalin enema revealed no macroscopic changes, and the groups with only formalin enema showed mild transient changes. The endotoxin level in the blood during the experiment increased (36 pg/ml) at 24 h after the treatment in the LPS-sensitized group, while non-sensitized control rabbits had higher levels of endotoxin. Though fibrinogen and PTT levels had increased at 24 and 72 h, these levels were marked in the control rabbits. The direct reaction of LPS was minimal, and local immune reaction by LPS seems to play an important role in the perpetuation of experimental colitis. Tissue fibrinolysis of the colon increased significantly as the mucosal damage appeared. This experimental colitis with LPS may be useful as a model of human ulcerative colitis.

PMID: 3961278 [PubMed - indexed for MEDLINE]

LPS has been found to be the culprit for causing Crohn's disease in patients who carry the NOD2 gene.

View this article in Medscape
(Excerpt from this website)
"Their findings therefore support the notion that patients with familial Crohn's disease are "genetically wired" to mount an intense immune response. In the presence of the appropriate initiating event, this genetic predisposing factor leads to nonspecific inflammation. Because of the mutation in the NOD2 gene in patients with Crohn's disease and the inability of monocytes to recognize LPS, the adaptive immune system responds with chronic, uncontrolled intestinal inflammation and destruction. In the future, additional genes that are involved in the altered recognition of bacterial cell wall products will likely be implicated in the pathogenesis of IBD as well."

View this article in PubMed
1: Acta Med Okayama. 1978 Jul;32(3):207-16.
A study of endotoxemia in ulcerative colitis and Crohn's disease. II. Experimental study.

* Aoki K.

The intestinal mucosal barrier of rabbits was damaged by carrageenan-induced ulceration of the colon, superior mesenteric artery occlusion (SMAO) and hemorrhagic shock and the values of Endotoxin (lipopolysaccharide, LPS) were determined by radioimmunoassay and the concentration of lysozyme (LZM) by the turbidimetric method. As a result, endotoxemia was observed in 13 out of 15 carrageenan rabbits, and in all of the SMAO and hemorrhagic shocked rabbits. Serum LZM concentration rose with time in all cases. As to the correlation of LPS and LZM, they changed almost in parallel in carrageenan rabbits, SMAO and hemorrhagic shock. LPS value and LZM concentration in blood were also determined in LPS injected rabbits. It was confirmed that injected LPS increased the LZM concentration of blood. On the basis of these results, it can be concluded that destruction of intestinal mucosal barrier permits an invasion of LPS into blood and then releases LZM into the blood stream.

PMID: 151486 [PubMed - indexed for MEDLINE]

Gut inflamation

View this article in PubMed
1: Transplant Proc. 2006 Jul-Aug;38(6):1815-7.Click here to read Links The role of dendritic cells in the gastrointestinal field effect.

* Koscielny A, * Boerner T, * Wehner S, * Kurts C, * Kalff JC.

Department of Surgery, University of Bonn Medical School, Sigmund-Freud-Strasse 25, D-53125 Bonn, Germany.

INTRODUCTION: Intestinal manipulation leads to local bowel wall inflammation that subsequently spreads over the entire gastrointestinal tract. Previously, this gastrointestinal field effect had been demonstrated by us in a rodent model. We herein postulated an immunologic mechanism mediated by activated leukocytes. The aim of this study was to investigate the activation, maturation and migration of dendritic cells (DC) of the intestinal smooth muscle following surgical trauma and i.p. lipopolysaccharide challenge. METHODS: Mice underwent standardized intestinal manipulation or iP LPS administration and tissues (intestinal muscularis, Peyer's patches, mesenteric lymph nodes, and spleen) were obtained at various times after manipulation. DC were isolated by tissue digestion and separated by CD11c-iMAG. The harvested DC were analyzed by FACS. The activation pattern of DC was analyzed by polymerase chain reaction. RESULTS: We found a significant increase in DC within the intestinal muscularis, the Peyer's patches and the mesenteric lymph nodes at 6 and 12 hours following intestinal manipulation and injection of LPS. There was an upregulation of the costimulatory molecules major histocompatibility complex II, CD40, CD80, CD86, and CD205 in the DC after intestinal manipulation. CCR-2, CCR-5, CCR-7, CCL-19, and interleukin-12a were upregulated in a time- and tissue-dependent manner. CONCLUSION: Intestinal manipulation or LPS challenge induced a recruitment of DC into the muscularis externa and mesenteric lymph nodes combined with an upregulation of costimulatory immunocompetent molecules and migratory surface markers in DCs. These findings demonstrate a precondition for an immunologic response and a possible immunologically mediated gastrointestinal field effect.

PMID: 16908290 [PubMed - indexed for MEDLINE]

Help for understanding the article about LPS causing a leaky gut. These definitions clarify the article that follows:

"Intestinal mucosal permeability" or just "permeability" are scientific terms which describe leakiness of the gut.



The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis.

LPS increases leaky gut.

The experimental group received an injection of lipopolysaccharide, while controls received an equivalent volume of saline solution; a third group received no treatment. It was found that the mice who were injected with LPS had an ileal mucosa that was more permeable (leaky) and permitted the movement of E coli across ileal mucosa much more than occurred for the mice that were not treated for LPS. The leaky gut of 78% of lipopolysaccharide-treated animals allowed the passage of E coli while the rate of untreated mice was only 14%.

View this article in PubMed
1: Arch Surg. 1995 Jan;130(1):53-8. Links The effect of endotoxin on intestinal mucosal permeability to bacteria in vitro.

* Go LL, * Healey PJ, * Watkins SC, * Simmons RL, * Rowe MI.

Department of Pediatric Surgery, Children's Hospital of Pittsburgh, Pa.

OBJECTIVE: To examine the role of the intestinal mucosa in bacterial translocation, in vitro bacterial passage across ileal mucosal segments mounted in Ussing chambers were studied in control and endotoxin (lipopolysaccharide)-treated rats. DESIGN: Experimental study. MATERIALS AND METHODS: Three groups of rats were studied. The experimental group received an intraperitoneal injection of lipopolysaccharide, while controls received an equivalent volume of saline solution; a third group received no treatment. Twenty-four hours later, all groups underwent laparotomy and organ culture to assess bacterial translocation. At the same time, a segment of mucosa from the terminal ileum of each animal was mounted in a Ussing chamber, and the transmucosal passage of labeled Escherichia coli from the luminal to serosal surface was assessed by results of serial cultures. RESULTS: In vivo bacterial translocation occurred in 100% of the lipopolysaccharide-treated animals, significantly higher than the incidence seen in controls (25%; P < .05). In vitro passage of labeled E coli across ileal mucosa in the Ussing chamber occurred in 78% of lipopolysaccharide-treated animals, while in controls transmucosal passage was seen in only 14% (P < .05). Histologic examination of mucosa from both groups using light and transmission electron microscopy demonstrated no structural differences between groups. CONCLUSIONS: Increased permeability to bacteria at the mucosal level contributes to the bacterial translocation seen in endotoxemia.

[Endotoxin is another name for LPS and endotoxemia is LPS poisoning.] PMID: 7802577 [PubMed - indexed for MEDLINE]

LPS and Digestive Malfunction

View this article in PubMed
J Clin Invest. 1988 November; 82(5): 1714�1721.

Bacterial lipopolysaccharide-induced intestinal microvascular lesions leading to acute diarrhea.

V I Mathan, G R Penny, M M Mathan, and D Rowley

Wellcome Research Unit, Christian Medical College Hospital, Vellore, India.

Subcutaneous challenge of mice with lipopolysaccharide (LPS) from gram negative bacteria, produced an intestinal microvascular lesion causing fluid exudation into the lumen of the intestine and diarrhea. The microvascular lesion was characterized by endothelial cell damage and microthrombi in the venules and capillaries of the intestinal lamina propria. Marker organisms, given orally to challenged mice, grew in the exuded fluid and could invade the mucosa. Intravenous transfer of postchallenge plasma produced the lesion in normal mice and absorption of such plasma by Sepharose coupled to LPS-antibody abolished this effect. Instillation of large quantities of LPS into the lumen of the intestine produced scattered microvascular lesions, although none of these animals developed diarrhea. Since a similar microvascular lesion has been described in the rectal mucosal lamina propria of adults with acute diarrhea, it is suggested that LPS-induced vascular damage may be a novel mechanism in the pathogenesis of acute diarrhea.

LPS disrupts gastrointestinal transit

View this article in PubMed
Gastrointestinal transit during endotoxemia: the role of nitric oxide.

Wirthlin DJ, Cullen JJ, Spates ST, Conklin JL, Murray J, Caropreso DK, Ephgrave KS.

Department of Surgery, University of Iowa College of Medicine, Iowa City, 52242, USA.

We hypothesized that the disrupted gastrointestinal transit that occurs during endotoxemia is mediated by nitric oxide (NO) and that the inhibition of NO synthesis will normalize intestinal transit and gastric emptying. To determine the effects of endotoxin and steroids on the activity of gastrointestinal smooth muscle NO synthase, rats underwent placement of an intravenous (iv) line and then were given Escherichia coli lipopolysaccharide (LPS) 10 mg/kg/iv; LPS, 10 mg/kg/iv + dexamethasone, 3 mg/kg/iv; or saline. The activity of nitric oxide synthase in the stomach, small intestine, and colon were determined by measuring the conversion of L-[3H]arginine to L-[3H]citrulline. To determine intestinal transit and gastric emptying, gavage feedings of nonabsorbable liquid markers were given and rats divided into eight groups: 0.9% NaCl, 1 ml/hr x 5 hr (control); LPS, 10 mg/kg/iv; LPS + N-omega-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg/hr x 5 hr; LPS + N-omega-nitro-D-arginine methyl ester (D-NAME), 10 mg/kg/hr x 5 hr; LPS + L-arginine, 100 mg/kg/hr x 5 hr; LPS + L+NAME + L-arginine; LPS + N-omega-nitro-L-arginine (L-NNA) 10 mg/kg/hr; or LPS + L-NNA + L-arginine. LPS increased the enzymatic activity of both the constitutive and the inducible forms of NO synthase in the small intestine and fundus of the stomach. The acceleration of intestinal transit produced by endotoxemia was reversed with both L-NAME and L-NNA but not with D-NAME. Endotoxemia slowed gastric emptying but this effect was not reversed with either L-NAME or L-NNA. We conclude that NO plays a major role in mediating the rapid intestinal transit during endotoxemia.

PMID: 8598659 [PubMed - indexed for MEDLINE]

View this article in PubMed
Effects of endotoxin on regulation of intestinal smooth muscle nitric oxide synthase and intestinal transit.

Cullen JJ, Mercer D, Hinkhouse M, Ephgrave KS, Conklin JL.

Department of Surgery, University of Iowa College of Medicine, Iowa City, USA.

BACKGROUND: The disrupted intestinal transit during endotoxemia may be mediated by nitric oxide (NO). We hypothesized that the isoforms of nitric oxide synthase (NOS) are up-regulated in intestinal smooth muscle during endotoxemia and that the scavenging of NO will normalize transit. METHODS: Rats were given Escherichia coli lipopolysaccharide (LPS) 10 mg/kg intravenously and were killed 4 hours later. To determine the activity of NOS isoforms in the jejunum and ileum, the conversion of tritiated L-arginine to tritiated L-citrulline was measured. Western immunoblots were performed by incubating the extracted protein with specific polyclonal antibodies. To determine intestinal transit, rats were divided into 4 groups: 0.9% sodium chloride 1 mL/h intravenously for 5 hours, LPS 10 mg/kg intravenous bolus plus 1 mL/h 0.9% sodium chloride intravenously, LPS plus oxyhemoglobin 0.5 g/kg/h intravenously, and oxyhemoglobin 0.5 g/kg/h intravenously. RESULTS: LPS increased the constitutive and inducible NOS enzyme activities in the jejunum and ileum. Western blots demonstrated that LPS up-regulates both the NOS1 and NOS2 isoforms in jejunal and ileal smooth muscle. Oxyhemoglobin alone increased intestinal transit compared with controls, whereas endotoxemia increased intestinal transit, which was ameliorated with infusions of oxyhemoglobin. CONCLUSIONS: NO may play a major role in mediating the rapid intestinal transit induced by endotoxemia.

PMID: 10076620 [PubMed - indexed for MEDLINE]

Constipation-predominant IBS patients and diarrhea-predominant IBS patients both demonstrated symptoms of Escherichia coli lipopolysaccharide (LPS)-induced *cytokine production.

Constipation-predominant IBS patients showed increased lipopolysaccharide (LPS)-induced IL-1beta levels compared with Healthy Controls and diarrhea-predominant IBS patients who showed an increase in all cytokine levels.

*cytokines-a group of proteins and peptides that are used in organisms as signaling compounds View this article in PubMed

1: Gastroenterology. 2007 Mar;132(3):913-20. Epub 2007 Jan 26. Links

Immune activation in patients with irritable bowel syndrome.

Liebregts T, Adam B, Bredack C, Roth A, Heinzel S, Lester S, Downie-Doyle S, Smith E, Drew P, Talley NJ, Holtmann G.

Department of Gastroenterology and Hepatology, University of Adelaide, Royal Adelaide Hospital, South Australia; Nerve-Gut Research Laboratory, Hanson Institute, Adelaide, SA, Australia.

Background & Aims: The objective was to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of pro inflammatory *cytokines. We also explored whether symptoms and psychiatric comorbidity in IBS are linked to the release of pro-inflammatory cytokines.

We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs).
PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (1 ng/mL) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6) was measured by enzyme-linked immunosorbent assay.

Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale.

IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients;constipation-predominant IBS patients showed increased LPS-induced IL-1beta levels compared with HCs.
Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than three bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .001) with anxiety in patients with IBS.

Conclusions: Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.

PMID: 17383420 [PubMed - in process]

LPS is linked to the problems of gluten,soy and dairy in ASD children. A famous experiment with ASD children found a correlation between the sensitivity for gliadin,soy and dairy and the children's reactions to LPS. The authors suggest that the root cause of the food protein sensitivity may be an underlying sensitivity to endotoxin or lipopolysaccharides (LPS) which comes from the surfaces of gram negative bacteria in the gut.

This is a very important since the elimination of gliadin,soy and dairy is the backbone of the GFCF diet. (gliadin is A glycoprotein (a carbohydrate plus a protein) within gluten. )

Below is the article by Jyonouchi that links LPS to dairy,gliadin and soy sensitivity. Elaine Gottschall's Comments on the Jyonouchi Paper

The abstract of Jyonouchi's paper says that children with autism spectrum disorder (ASD) frequently reveal various gastrointestinal (GI) symptoms that may resolve with an elimination diet along with apparent improvement of some of the behavorial symptoms. Evidence suggests that ASD may be accompanied by aberrant (inflammatory) innate immune responses. THIS MAY PREDISPOSE ASD CHILDREN TO SENSITIVIES TO COMMON DIETARY PROTEINS LEADING TO GI INFLAMMATION AND AGGRAVATION OF SOME BEHAVIORAL SYMPTOMS."

The authors demonstrate conclusively that there is an abnormal immune response to cow's milk protein and wheat protein (gliadin) and soy in ASD. What is interesting is that the diet model is NOT THE SAME AS THE OPIOID MODEL BUT IS BASED ON A VARIABLE IMMUNE RESPONSE IN WHICH NOT EVERY CHILD WILL SHOW SENSITIVITY TO EVERY FOOD. But the punch line is: The authors suggest that the root cause of the food protein sensitivity may be an underlying sensitivity to endotoxin or lipopolysaccharides (LPS) which comes from the surfaces of gram negative bacteria in the gut.

Summary: This response to the bacterial endotoxin (LPS) PREDISPOSES THESE CHILDREN TO SENSITIZATION TO DIETARY PROTEINS. This is consistent with a model of abnormal gut flora development that promotes immune response to gut bacteria. This means that ASD kids may develop a kind of autoimmunie response to their own gut flora.
(Some of these comments were written by Mark Blaxhill.)

The Jyonouchi Paper

*Neuropsychobiology. 2002;46(2):76-84)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&list_uids=12378124&dopt=Abstract

Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder.

Jyonouchi H, Sun S, Itokazu N.

Department of Pediatrics, University of Minnesota, Minneapolis, Minn, USA.

OBJECTIVES: Children with autism spectrum disorder (ASD) frequently reveal various gastrointestinal (GI) symptoms that may resolve with an elimination diet along with apparent improvement of some of the behavioral symptoms. Evidence suggests that ASD may be accompanied by aberrant (inflammatory) innate immune responses. This may predispose ASD children to sensitization to common dietary proteins (DP), leading to GI inflammation and aggravation of some behavioral symptoms.

METHODS: We measured IFN-gamma, IL-5, and TNF-alpha production against representative DPs [gliadin, cow's milk protein (CMP), and soy] by peripheral blood mononuclear cells (PBMCs) from ASD and control children [those with DP intolerance (DPI), ASD siblings, and healthy unrelated children]. We evaluated the results in association with proinflammatory and counter-regulatory cytokine production with endotoxin (LPS), a microbial product of intestinal flora and a surrogate stimulant for innate immune responses. RESULTS: ASD PBMCs produced elevated IFN-gamma and TNF-alpha, but not IL-5 with common DPs at high frequency as observed in DPI PBMCs.

ASD PBMCs revealed increased proinflammatory cytokine responses with LPS at high frequency with positive correlation between proinflammatory cytokine production with LPS and IFN-gamma and TNF-alpha production against DPs. Such correlation was less evident in DPI PBMCs. CONCLUSION: Immune reactivity to DPs may be associated with apparent DPI and GI inflammation in ASD children that may be partly associated with aberrant innate immune response against endotoxin, a product of the gut bacteria. Copyright 2002 S. Karger AG, Basel

PMID: 12378124 [PubMed - indexed for MEDLINE]

[Endotoxin is another name for LPS and endotoxemia is LPS poisoning. IMBF is intestinal microvascular blood flow ] View this article in PubMed
1: Clin Hemorheol Microcirc. 2003;28(4):209-20.

Sympathetic modulation of intestinal microvascular blood flow oscillations in experimental endotoxemia.

Birnbaum J, Lehmann C, Stauss HM, Weber M, Georgiew A, Lorenz B, Pulletz S, Grundling M, Pavlovic D, Wendt M, Kox WJ.

Klinik fur Anasthesiologie und operative Intensivmedizin, Humboldt-Universitat zu Berlin, Schumannstr. 20/21, 10117 Berlin, Germany.

Impairment of the intestinal microcirculation has been recognized as an important factor in the pathogenesis of endotoxin related sepsis syndrome. We investigated the effects of endotoxemia on the variability of intestinal microvascular blood flow (IMBF ) and arterial blood pressure (BP) in a prospective, randomized, controlled animal study. Recordings of IMBF (laser Doppler fluxmetry) and BP were performed before, two and four hours after i.v. injection of either placebo or endotoxin (5 mg/kg b.w. lipopolysaccharide from E. coli, serotype O55:B5). Control experiments were performed with systemic (clonidine) and local intestinal (surgery) sympathectomy. Spectral analysis was performed using the autoregressive approach. Spectral power was determined in two frequency bands (low frequency (LF): 0.27-0.74 Hz; high frequency (HF): 0.76-3.00 Hz). Two hours after endotoxin challenge a significant decrease in IMBF was observed. LF spectral power of IMBF and BP increased significantly in the endotoxin challenged group, while no effects were observed in the placebo group. Four hours after endotoxin administration IMBF decreased further and LF spectral power of IMBF and BP remained elevated. Denervation prevented the decrease in IMBF but did not abolish the LF power increase. Clonidine administration attenuated the IMBF decrease and significantly diminished the increase in LF spectral power of IMBF and BP. We conclude that endotoxemia is associated with increased sympathetic outflow to the systemic vasculature, as indicated by the increase in LF spectral power of arterial blood pressure. The increase in LF variability of IMBF is secondary to the increase in LF spectral power of BP, since it could be attenuated by systemic and not by local intestinal sympathectomy.

PMID: 12897412 [PubMed - indexed for MEDLINE]

*cytokines-a group of proteins and peptides that are used in organisms as signaling compounds