The pleiotropic cytokine interleukin-6 (IL-6) controls both the peripheral and central components of the acute-phase response. These activities are mediated via the IL-6 membrane receptor, but probably also via agonistic soluble IL-6 receptors (sIL-6Rs). In the present study we conducted dose-response experiments with rats that were intracerebroventricularly i.c.v.) injected with recombinant human IL-6 and sIL-6R and determined body temperature, locomotor activity, food intake, and water consumption using radiotelemetry and continuous recordings of feeding and drinking. IL-6 injected i.c.v. at 1, 10, and 100 ng increased body temperature and decreased locomotor activity and food intake, but it did not affect water consumption. When 10 ng sIL-6R, which lacked detectable biological activity, was injected i.c.v. 1 h before 1 ng IL-6, the central effects of IL-6 were enhanced and prolonged, and this was not due to endotoxin contamination of the recombinant proteins. Our data suggest that IL-6 plays an important role in the regulation of body temperature, general activity, and food intake in sick animals. Moreover, we have shown for the first time that it is possible to potentiate the effects of a mediator in vivo by administration of the corresponding receptor, which is a novel pharmacological tool for increasing receptor capacity.

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Background: Chronic inflammation from any source is associated with increased cardiovascular risk. Periodontitis is a possible trigger of chronic inflammation. We investigated the possible association between periodontitis and coronary heart disease (CHD), focusing on microbiological aspects.Methods: A total of 789 subjects (263 patients with angiographically confirmed, stable CHD and 526 populationbased, age-and sex-matched controls without a history of CHD) were included in the Coronary Event and Periodontal Disease (CORODONT) study. Subgingival biofilm samples were analyzed for periodontal pathogens Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola using DNA-DNA hybridization. The need for periodontal treatment in each subject was assessed using the Community Periodontal Index of Treatment Needs (CPITN). The main outcome measures included total periodontal pathogen burden, number of the vari-ous periodontal pathogens in the subgingival biofilm, and periodontal treatment needs (according to the CPITN).Results: In multivariable analyses, we found a statistically significant association between the periodontal pathogen burden (log 10 of the sum of all pathogens) (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.34-2.74; PϽ.001) or the number of A actinomycetemcomitans in periodontal pockets (log 10 ) (OR, 2.70; 95% CI, 1.79-4.07; PϽ.001) and the presence of CHD. In addition, a statistically significant association between an increase in mean CPITN score by 1 and the presence of CHD (OR, 1.67; 95% CI, 1.08-2.58; P =.02) was observed.Conclusions: Our findings suggest an association between periodontitis and presence of CHD. Periodontal pathogen burden, and particularly infection with A actinomycetemcomitans, may be of special importance.

Based on previous results showing the expression of ameloblastin (Ambn; amelin) in the formation of mesenchymal dental hard tissues, we investigated its presence during bone development. Immunohistochemistry (IHC), in situ hybridization (ISH), and reverse transcription-polymerase chain reaction (RT-PCR) were used to investigate the expression of ameloblastin protein and mRNA during craniofacial development in rats. Tissue samples were collected on embryonic day 18 and from days 2-28 postnatally. IHC revealed the expression of ameloblastin during bone formation at embryonic and early postnatal stages with different patterns of expression in intramembranous and endochondral ossification. In intramembranous ossification, ameloblastin expression was detected in the superficial layer of the condensed vascularized primitive connective tissue and in the cellular layer covering the surface of the newly formed woven bone. In endochondral ossification, ameloblastin was expressed within the extracellular matrix of the cartilage templates and in the perichondrium. Between days 2 and 28 the expression decreased markedly, concordant with the maturation of the bone, and disappeared after completion of bone remodeling. The results obtained by IHC were confirmed by ISH and RT-PCR, showing the expression of ameloblastin mRNA during craniofacial bone formation. This study indicates the expression of the putative dental protein ameloblastin during craniofacial bone development in rats.

Ameloblastin (Ambn, also named "amelin" or "sheathlin") is a protein participating in enamel formation and mesenchymal-ectodermal interaction during early dentin formation in developing teeth. Experiments have demonstrated an association between Ambn expression and healing of acute pulp wounds. The purpose of this study was to investigate if local application of recombinant fusion Ambn (rAmbn) could influence reparative dentin formation in pulpotomized teeth. In this randomized, double-blinded study, pulpotomy was performed in 28 lower central incisors in 17 adult miniature pigs. Following the surgical procedure, the exposed pulp tissue was covered either with rAmbn or with calcium hydroxide. After 2, 4, or 8 weeks, the teeth were extracted and examined by histomorphometry and immunohistochemistry using antibodies against porcine ameloblastin, collagen type I, and dentin sialoprotein (DSP). In rAmbn-treated teeth, a substantial amount of newly formed reparative dentin was observed at the application site, completely bridging the pulpal wound. Dentin formation was also observed in calcium hydroxide-treated teeth; however, the amount of reparative dentin was significantly smaller (P < 0.001) than after rAmbn treatment. Immunohistochemistry confirmed that the new hard tissue formed was similar to dentin. This is the first time a direct link between ameloblastin and dentin formation has been made in vivo. The results suggest potential for rAmbn as a biologically active pulp-dressing agent for enhanced pulpal wound healing and reparative dentin formation after pulpotomy procedures.