IL-18-binding protein (IL-18BP) is a natural IL-18 inhibitor. Human IL-18BP isoform a was produced as fusion construct with human IgG1 Fc and assessed for binding and neutralizing IL-18. IL-18BP-Fc binds human, mouse, and rat IL-18 with high affinity (KD 0.3–5 nM) in a BIAcore-based assay. In vitro, IL-18BP-Fc blocks IL-18 (100 ng/ml)-induced IFN-γ production by KG1 cells (EC50 = 0.3 μg/ml). In mice challenged with an LD90 of LPS (15 mg/kg), IL-18BP-Fc (5 mg/kg) administered 10 min before LPS blocks IFN-γ production and protects against lethality. IL-18BP-Fc administered 10 min before LPS blocks IFN-γ production induced by LPS (5 mg/kg) with ED50 of 0.005 mg/kg. Furthermore, IL-18BP-Fc (5 mg/kg) abrogates LPS (5 mg/kg)-induced IFN-γ production even when administered 6 days before LPS but shows no effect when administered 9 or 12 days before LPS. Given 10 min before LPS challenge to mice primed 12 days in advance with heat-killed Propionibacterium acnes, IL-18BP-Fc prevents LPS-induced liver damage and IFN-γ and Fas ligand expression. Given at the moment of priming with P. acnes, IL-18BP-Fc decreases P. acnes-induced granuloma formation, macrophage-inflammatory protein-1α and macrophage-inflammatory protein-2 production and prevents sensitization to LPS. IL-18BP-Fc also prevents Con A-induced liver damage and IFN-γ and Fas ligand expression as well as liver damage induced by Pseudomonas aeruginosa exotoxin A or by anti-Fas agonistic Ab. In conclusion, IL-18BP can be engineered and produced in recombinant form to generate an IL-18 inhibitor, IL-18BP-Fc, endowed with remarkable in vitro and in vivo properties of binding and neutralizing IL-18.

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There is an acute need for effective therapy for inflammatory bowel disease (IBD), particularly at the level of repair of the damaged epithelium. We evaluated the efficacy of recombinant human keratinocyte growth factor (rHuKGF) in both the dextran sodium sulfate (DSS) and the CD4(+)CD45RB(Hi) T cell transfer models of IBD. Disease was induced either by the ad libitum administration to normal mice of 4% DSS in the drinking water or by the injection of 4 x 10(5) CD4(+)CD45RB(Hi) T cells into immunodeficient scid/scid mice. rHuKGF was administered by subcutaneous injection at doses of 1.0 or 3.0 mg/kg in both preventative and therapeutic regimens during both studies. rHuKGF significantly improved survival and body weight loss in the DSS model in both preventative and therapeutic dosing regimens. It also improved diarrhea, hematochezia, and hematological parameters, as well as large intestine histopathology. In the T cell transfer model, rHuKGF improved body weight loss, diarrhea, and levels of serum amyloid A, as well as large intestine histopathology. In both models of IBD, the colonic levels of intestinal trefoil factor (ITF) were elevated by the disease state and further elevated by treatment with rHuKGF. These data suggest that rHuKGF may prove useful in the clinical management of IBD and its effects are likely mediated by its ability to locally increase the levels of ITF.

Aim:The genus Astyanax is one of the richest in number of species and has one of the widest geographical distributions in Argentina, being possible to find in nine ichthyogeographic ecoregions. The aim of the present work was to analyze the population structure of Astyanax fasciatus in the Garupá Stream, Province of Misiones, Argentina, considering its distribution by size, standard length-total weight relationship and aspects of its reproductive and feeding biology; Methods: A total of eight experimental fishing campaigns were carried out between September 2002 and May 2004, in agreement with the seasons of the year, using a set of gillnets; Results: We captured a total of 386 individuals, 70% of which in the Middle Basin in autumn and winter. The following gonad stages were identified in both males and females: resting, maturing, mature and spawning. The highest gonadal activity corresponded to the autumn-winter period. The Middle Basin showed the highest capture of individuals in reproductive activity, thus reflecting the seasonality of spawning. The average fecundity was of 4000 oocytes, being 1100 μm the largest oocyte diameter. The mean standard length of the total catch was 99.3 mm and females reached larger sizes than males (P < 0.05). The standard length varied according to the seasons of the year. Both sexes presented an isometric growth (b = 3). Females presented the highest values of K in spring and summer, whereas males did so in spring. The K-GSI relationship reflected that the highest K values corresponded to the lowest GSI ones. We found that A. fasciatus feeds on a wide variety of foods of both plant and animal origin. The food items of plant origin presented the highest index of occurrence; Conclusions: The long spawning seasons and the recruitment along all four seasons of the year allow characterizing A. fasciatus as a foraging species that is very well adapted to the environment studied in this work.Keywords: Astyanax fasciatus, population, reproduction, feeding, Garupa Stream.Resumo: Objetivo: O gênero Astyanax é um dos mais ricos em número de espécies e tem uma das maiores distribuições geográficas na Argentina, sendo possível encontrar em nove ecorregiões ictiogeográfica. O objetivo do presente trabalho foi analisar a estrutura populacional de Astyanax fasciatus no arroio Garupá, Província de Misiones, na Argentina, considerando a sua distribuição por tamanho, relação peso-padrão de comprimento total e aspectos de sua biologia reprodutiva e alimentação; Métodos: Foram realizadas oito operações de pescaria sazonais, entre setembro de 2002 e maio de 2004, com uma bateria de redes de emalhar; Resultados: Foram capturados 386 indivíduos, 70% na Bacia Média no outono e inverno. Foram identificadas as seguintes etapas de maduração gonadal em ambos os sexos: repouso, maturação, maduro e desova. A maior atividade gonadal correspondeu ao período de outono-inverno. A Bacia do Médio apresentou a maior captura de indivíduos em atividade reprodutiva, refletindo a sazonalidade da desova. À fe...

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