TREM-1--expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases

Triggering receptor expressed on myeloid cells-1 (TREM-1) potently amplifies acute inflammatory responses by enhancing degranulation and secretion of proinflammatory mediators. Here we demonstrate that TREM-1 is also crucially involved in chronic inflammatory bowel diseases (IBD). Myeloid cells of the normal intestine generally lack TREM-1 expression. In experimental mouse models of colitis and in patients with IBD, however, TREM-1 expression in the intestine was upregulated and correlated with disease activity. TREM-1 significantly enhanced the secretion of relevant proinflammatory mediators in intestinal macrophages from IBD patients. Blocking TREM-1 by the administration of an antagonistic peptide substantially attenuated clinical course and histopathological alterations in experimental mouse models of colitis. This effect was also seen when the antagonistic peptide was administered only after the first appearance of clinical signs of colitis. Hence, TREM-1-mediated amplification of inflammation contributes not only to the exacerbation of acute inflammatory disorders but also to the perpetuation of chronic inflammatory disorders. Furthermore, interfering with TREM-1 engagement leads to the simultaneous reduction of production and secretion of a variety of pro-inflammatory mediators such as TNF, IL-6, IL-8 (CXCL8), MCP-1 (CCL2), and IL-1beta. Therefore, TREM-1 may also represent an attractive target for the treatment of chronic inflammatory disorders.

[Prevalence of hereditary diseases in three-year-old Swiss Warmblood horses]

The objective of this study was to investigate clinical signs indicating hereditary diseases like equine sarcoid, osteochondrosis (OC) and the idiopathic laryngeal hemiplegia (ILH), and to demonstrate relationships between environment, feeding habits and conformation ("exterieur" evaluation) of the horses. For this purpose, we analyzed veterinary examinations of 403 stallions at the approvals since 1994 examined 493 three-year-old Swiss Warmblood horses, which were shown at the Swiss-Field-Tests in 2005.With the help of the owners a questionnaire on health, environment and feeding habits of the animals was completed. At the same time, the horses were assessed and graded for their "exterieur" (type, conformation, gaits) by judges of the Swiss Sporthorse breeding association. In 11.5% of horses sarcoids were found, 8.7% showed one and 2.8% several tumors.The prevalence of sarcoids in offspring of sires with known sarcoids was not significantly higher than in descendants from stallions without a known history of sarcoids. We found distended joints as a possible symptom of OC in 11.4% of the horses, 3.9% (n = 19) in both tarsal joints.We did not find a relationship between enlarged joints in the offspring and the presence of OC in the sires. Abnormal respiratory noise at work, as a possible sign for ILH, was heard only in 1.2% (n = 6). It is important to note that while we found a high number of sarcoid affected horses compared to other studies, presence of enlarged joints was not very frequent and very few horses showed abnormal respiratory noise. Additionally, we found no correlation between "exterieur" marks and the horse's general health.

Herbal medicine in the treatment of liver diseases

Herbal drugs have become increasingly popular and their use is widespread. Licensing regulations and pharmacovigilance regarding herbal products are still incomplete and clearcut proof of their efficacy in liver diseases is sparse. Nevertheless, a number of herbals show promising activity including silymarin for antifibrotic treatment, phyllantus amarus in chronic hepatitis B, glycyrrhizin to treat chronic viral hepatitis, and a number of herbal combinations from China and Japan that deserve testing in appropriate studies. Apart from therapeutic properties, reports are accumulating about liver injury after the intake of herbals, including those advertised for liver diseases. Acute and/or chronic liver damage occurred after ingestion of some Chinese herbs, herbals that contain pyrrolizidine alkaloids, germander, greater celandine, kava, atractylis gummifera, callilepsis laureola, senna alkaloids, chaparral and many others. Since the evidence supporting the use of botanicals to treat chronic liver diseases is insufficient and only few of them are well standardised and free of potential serious side effects, most of these medications are not recommended outside clinical trials. Particularly with regard to the latter, adequately powered randomised-controlled clinical trials with well-selected end points are needed to assess the role of herbal therapy for liver diseases.

[Anti-interleukin-5 therapy for eosinophilic diseases]

In a number of diseases with eosinophilia, elevated interleukin (IL)-5 levels are detected in the peripheral blood and/or tissues. IL-5 plays an important role in regulating the production, differentiation, recruitment, activation, and survival of eosinophils. Therefore, neutralizing IL-5 by blocking antibodies seems a promising approach in the treatment of eosinophilic diseases. Clinical trials have demonstrated that anti-IL-5 therapy results in a rapid decrease in peripheral blood eosinophil numbers. Moreover, improvement of symptoms in patients with lymphocytic variants of hypereosinophilic syndromes, in eosinophilic esophagitis and chronic rhinitis with nasal polyposis has been observed. In contrast, in patients with bronchial asthma or atopic eczema, anti-IL-5 therapy showed only moderate or no clinical effects. Future studies will have to identify those eosinophilic diseases in which anti-IL-5 antibodies are effective, perhaps with the help of newly developed biomarkers.

8-Isoprostane in nasally exhaled breath condensate in different pediatric lung diseases

OBJECTIVE: Increased levels of 8-isoprostane were found in various human lung diseases suggesting 8-isoprostane as a marker of pulmonary oxidative stress in vivo. The exact role in pediatric lung diseases has not been defined yet. The goal of this study was to clarify the role of 8-isoprostane in nasally exhaled breath condensate as possible marker of oxidative stress in children with different lung diseases. METHODS: Levels of 8-isoprostane were measured in nasally exhaled breath condensate of 29 cystic fibrosis patients, 19 children with a history of wheezing episodes, 8 infants with acute respiratory tract infection and 53 healthy subjects using a specific enzyme immunoassay. RESULTS: Levels of 8-isoprostane did neither discriminate between different disease groups nor correlate with lung function in cystic fibrosis patients. CONCLUSIONS: Levels of 8-isoprostane in nasally exhaled breath condensate do not reflect oxidative stress in children with different lung diseases.

Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases

The antioxidant properties of tryptophan and some of its oxidative metabolites were examined by measuring how efficiently they inhibited peroxyl radical-mediated oxidation of phosphatidylcholine liposomes and B-phycoerythrin. Low micromolar concentrations of 5-hydroxytryptophan, 3-hydroxykynurenine, xanthurenic acid, or 3-hydroxyanthranilic acid, but not their corresponding nonhydroxylated metabolic precursors, scavenged peroxyl radicals with high efficiency. In particular, 3-hydroxykynurenine and 3-hydroxyanthranilic acid protected B-phycoerythrin from peroxyl radical-mediated oxidative damage more effectively than equimolar amounts of either ascorbate or Trolox (a water-soluble analog of vitamin E). Enzyme activities involved or related to oxidative tryptophan metabolism, as well as endogenous concentrations of tryptophan and its metabolites, were determined within tissues of mice suffering from acute viral pneumonia. Infection resulted in a 100-fold induction of pulmonary indoleamine 2,3-dioxygenase (EC 1.13.11.17) as reported [Yoshida, R., Urade, Y., Tokuda, M. ; Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. This was accompanied by a 16- and 3-fold increase in the levels of lung kynurenine and 3-hydroxykynurenine, respectively. In contrast, endogenous concentrations of tryptophan and xanthurenic acid did not increase and 3-hydroxyanthranilic acid could not be detected. The activity of the superoxide anion (O2-.)-producing enzyme xanthine oxidase increased 3.5-fold during infection while that of the O2-.-removing superoxide dismutase decreased to 50% of control levels. These results plus the known requirement of indoleamine 2,3-dioxygenase for superoxide anion for catalytic activity suggest that viral pneumonia is accompanied by oxidative stress and that induction of indoleamine 2,3-dioxygenase may represent a local antioxidant defence against this and possibly other types of inflammatory diseases.

Host condition and host immunity affect parasite fitness in a bird-ectoparasite system

1. Parasites might preferentially feed on hosts in good nutritional condition as such hosts provide better resources for the parasites' own growth, survival and reproduction. However, hosts in prime condition are also better able to develop costly immunological or physiological defence mechanisms, which in turn reduce the parasites' reproductive success. The interplay between host condition, host defence and parasite fitness will thus play an important part in the dynamics of host-parasite systems.;2. In a 2 x 2 design, we manipulated both the access to food in great tit Parus major broods and the exposure of the nestlings to hen fleas Ceratophyllus gallinae, a common ectoparasite of hole-breeding birds. We subsequently investigated the role of manipulated host condition, host immunocompetence, and experimentally induced host defence in nestlings on the reproductive success of individual hen flea females.;3. The food supplementation of the nestlings significantly influenced the parasites' reproductive success. Female fleas laid significantly more eggs when feeding on food-supplemented hosts.;4. Previous parasite exposure of the birds affected the reproductive success of fleas. However, the impact of this induced host response on flea reproduction depended on the birds' natural level of immunocompetence, assessed by the phytohaemagglutinin (PHA) skin test. Flea fecundity significantly decreased with increasing PHA response of the nestlings in previously parasite-exposed broods. No relationship between flea fitness and host immunocompetence was, however, found in previously unexposed broods. The PHA response thus correlates with the nestlings' ability to mount immunological or physiological defence mechanisms against hen fleas. No significant interaction effect between early flea exposure and food supplementation on the parasites' reproductive success was found.;5. Our study shows that the reproductive success of hen fleas is linked to the hosts' food supply early in life and their ability to mount induced immunological or physiological defence mechanisms. These interactions between host quality and parasite fitness are likely to influence host preference, host choice and parasite virulence and thus the evolutionary dynamics in host-parasite systems.

Maternal modulation of natal dispersal in a passerine bird: An adaptive strategy to cope with parasitism?

The decision of how far to disperse from the natal territory has profound and long-lasting consequences for young animals, yet the optimal dispersal behavior often depends on environmental factors that are difficult or impossible to assess by inexperienced juveniles. Natural selection thus favors mechanisms that allow the adaptive and flexible adjustment of the offspring's dispersal behavior by their parents via either paternal or maternal effects. Here we show that different dispersal strategies maximize the reproductive success of young great tits (Parus major) originating from a parasite-infested or a parasite-free nest and demonstrate that differential transfer of maternal yolk androgens in response to parasitism can result in a modification of the offspring's dispersal behavior that appears adaptive. It demonstrates that prenatal maternal effects are an important yet so far neglected determinant of natal dispersal and highlights the potential importance of maternal effects in mediating coevolutionary processes in host-parasite systems.