Objective: Periodontitis is an infectious disease leading to inflammation and destruction of tissue surrounding and supporting the tooth. The progress of the inflammatory response depends on the host’s immune system and risk factors such as stress. The aim of the present study was to investigate the role of the endocannabinoid anandamide (AEA) in experimental periodontitis with restraint stress, since the endocannabinoid system is known to modulate the hypothalamo-pituitary-adrenal axis as well as immune functions and has been found in human gingival tissues. Methods: Experimental periodontitis was induced by ligature around first inferior molars and immobilization stress for 2 h twice daily for 7 days in a rat model. Results: Corticosterone plasma levels, locomotor activity, adrenal gland weight and bone loss were increased in periodontitis and stress groups, and there was also less weight gain. The inflammatory parameters such as prostaglandin E₂ (radioimmunoassay), nitric oxide (radioconversion of ¹⁴C-arginine), tumor necrosis factor (TNF)-α (ELISA) and interleukin (IL)-1β (Western blot) measured in the gingival tissue were significantly increased in the periodontitis groups compared to the control group. Local injection of AEA (10^–8M, 30 µl) decreased corticosterone plasma levels and the content of the cytokines TNF-α and IL-1β in gingival tissue in periodontitis-stress groups. These AEA-induced inhibitions were mediated by CB₁ and CB₂ cannabinoid receptors since the injection of both antagonists together, AM251 (10^–6M) and AM630 (10^–6M) in 30 µl, prevented these effects. Conclusion: The endocannabinoid AEA diminishes the inflammatory response in periodontitis even during a stressful situation.

No abstract

The pathogenesis of atherosclerosis includes the assignment of a critical role to cells of the monocyte/macrophage lineage and to pro-inflammatory cytokines. Niacin is known to improve lipid metabolism and to produce beneficial modification of cardiovascular risk factors. The aim of this work was to investigate if Niacin is able to modulate pro-inflammatory cytokine production in macrophages in a murine model of atherosclerosis. For this purpose C57Bl/6J mice fed with atherogenic diet (AGD) or with conventional chow diet were used. The AGD group showed an increase in body weight and in total plasma cholesterol, with no differences in triglyceride or HDL levels. Lesions in arterial walls were observed. The characterization of Niacin receptor showed an increase in the receptor number of macrophages from the AGD group. Macrophages from control and AGD animals treated in vitro with an inflammatory stimulus showed elevated levels of IL-6, IL-1 and TNF-α, that were even higher in macrophages from AGD mice. Niacin was able to decrease the production of pro-inflammatory cytokines in stimulated macrophages. Similar effect of Niacin was observed in an in vivo model of inflammation. These results show an attenuating inflammatory mechanism for this therapeutic agent and would point out its potential action in plaque stabilization and in the prevention of atherosclerosis progression. Furthermore, the present results provide the basis for future studies on the potential contribution of Niacin to anti-inflammatory therapies.

The hypothalamo-neurohypophyseal system plays a role in homeostasis under a variety of stress conditions, including endotoxemia. Oxytocin (OXT) and vasopressin (VP) are important hormones synthesized by neurons in the hypothalamic paraventricular and supraoptic nuclei and released into different brain regions and from the neurohypophyseal terminals into the blood in response to many patho-physiological stimuli. However, the mechanism that controls OXT and VP secretion has not been fully elucidated. Nitric oxide (NO) is a known mediator that regulates the release of these hormones. The endocannabinoid system is a new intercellular system that modulates several neuroendocrine actions. Endocannabinoids (eCB) are released as retrograde messengers by many neurons, including hypothalamic magnocellular neurons and cannabinoid receptors are localized within these neurons, as well as in the anterior and posterior pituitary lobes, suggesting an eCB role in the production and release of OXT and VP. Lipopolysaccharide (LPS) injection is a model used as immune challenge. LPS causes a neuroendocrine response that is mediated by cytokines, tumor necrosis factor-α being one of them. We focused on NO and endocannabinoid system participation on OXT and VP production and secretion during basal and stress conditions and found that eCB affect basal OXT and VP secretion by acting differently at each level of the hypothalamo-neurohypophyseal system. After LPS, there is an increase in eCB synthesis that enhances OXT secretion.