We have evaluated the role of prostaglandin E2 (PGE2) in the synthesis of nitric oxide (NO) by the activation of the inducible form of nitric oxide synthase (NOS) in the murine macrophage cell line, ...J774, stimulated with different doses of lipopolysaccharide (LPS). The stimulation of the J774 line with suboptimal doses of LPS (0.1 microgram/mL) caused a production of endogenous PGE2 that was capable of stimulating NOS activity inducing an increase in the NO synthesis, as attested by the fact that cyclooxygenase enzyme inhibitor, indomethacin, significantly reduced NO secretion. On the contrary, a higher dose of LPS (1 microgram/mL) produced high levels of PGE2 that reduced the levels of NOS and, subsequently, NO production. Experiments carried out with exogenous PGE2 indicated that concentrations between 1 and 10 ng/mL are able to stimulate the expression of NOS and the release of NO, while higher concentrations (> 50 ng/mL) are inhibitory. Furthermore, our data indicate that there is a network of interaction which involves NO, PGE2, and tumor necrosis factor. High levels of PGE2 inhibited TNF alpha secretion, which in turn could exert inhibitory effects on NO synthesis.
Background: Hepatitis A virus (HAV) circulation in the environment is decreasing in most industrialized Western countries. This decrease has lead to low seroprevalence rates in adults. As a ...consequence, many nonimmune unprotected travelers from areas of low prevalence are considered at risk of acquiring HAV infection when traveling to high HAV endemic areas in developing countries. The recent HAV inactivated vaccine has proved safe and effective, and its use in different geographic areas should be guided by local age-specific HAV seroprevalence rates. The aim of this paper is to describe the age-specific sero-epidemiology of HAV infection in travelers from a highly industrialized region in Northern Italy (Lombardy). Methods: Seven hundred and forty-four consecutive travelers aged from 20 to 59 years, subdivided in 10-year age groups, gave blood samples in the collaborative Health Centers in the Lombardy region and sera were tested for HAV IgG antibodies. A questionnaire was given to travelers that investigated alimentary habits and a history of previous travel. Results: Anti-HAV seroprevalence was 18.0%, 58.0%, 75.8%, and 89.5% in the 20-29, 30-39, 40-49, and 50-59 age groups, respectively. Age was the single most important determinant of anti-HAV seroprevalence. The influence of previous travels, eating shellfish, or ingestion of self-cultivated vegetables was ruled out by multivariate analysis. Conclusions: In the Lombardy region (Northern Italy), age specific anti-HAV seroprevalence rates are much higher than those reported in other Western European countries. The cost-benefit analysis suggested that travelers born after 1960 do not need serologic screening before vaccination. Whenever possible, however, HAV serologic screening is advisable for travelers born before 1960. However, the severity of the disease in older subjects, and the proved safety of HAV vaccination in immune subjects, may advise d'emblée HAV vaccination without prior screening, when serologic investigation is unfeasible because of lack of time or the unavailability of testing facilities.
The effect of an immunomodulator drug thymopentin (TP5) on the production of various cytokines (IFN-gamma, IL-2, IL-4, TNF-alpha) in mice of different ages has been studied. TP5 enhanced IL-2, ...TNF-alpha and IFN-gamma production but reduced the IL-4 secretion by splenocytes from aged mice (greater than 120 week old) in vitro. However, it had no effect on the IL-2, IFN-gamma, TNF-alpha or IL-4 production by splenocytes from young and adult mice. TP5 injected subcutaneously was able to induce high levels of IL-2 production by splenocytes from all groups of mice. The TP5 effect on TNF-alpha and IFN-gamma was similar, even though it was significant only in old mice. Furthermore, TP5 was able to significantly reduce IL-4 production in old mice, which normally produced high levels of this cytokine after mitogen stimulation. Since it has been observed in the mouse that the Th1 cells secrete IFN-gamma and IL-2, whereas the Th2 cells preferentially produce IL-3, IL-4 and IL-5, these results indicate that the immunopotentiatory activity of TP5 is due to the preferential up-regulation of Th1 cells.
We have evaluated the role of prostaglandin E
2 (PGE
2) in the synthesis of nitric oxide (NO) by the activation of the inducible form of nitric oxide synthase (NOS) in the murine macrophage cell ...line, J774, stimulated with different doses of lipopolysaccharide (LPS). The stimulation of the J774 line with suboptimal doses of LPS (0.1 μg/mL) caused a production of endogenous PGE
2 that was capable of stimulating NOS activity inducing an increase in the NO synthesis, as attested by the fact that cyclooxygenase enzyme inhibitor, indomethacin, significantly reduced NO secretion. On the contrary, a higher dose of LPS (1 μg/mL) produced high levels of PGE
2 that reduced the levels of NOS and, subsequently, NO production. Experiments carried out with exogenous PGE
2 indicated that concentrations between 1 and 10 ng/mL are able to stimulate the expression of NOS and the release of NO, while higher concentrations (>50 ng/mL) are inhibitory. Furthermore, our data indicate that there is a network of interaction which involves NO, PGE
2, and tumor necrosis factor. High levels of PGE
2 inhibited TNFα secretion, which in turn could exert inhibitory effects on NO synthesis.
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