Mucosal Lipocalin 2 Has Pro-Inflammatory and Iron-Sequestering Effects in Response to Bacterial Enterobactin

Nasal colonization by both gram-positive and gram-negative pathogens induces expression of the innate immune protein lipocalin 2 (Lcn2). Lcn2 binds and sequesters the iron-scavenging siderophore enterobactin (Ent), preventing bacterial iron acquisition. In addition, Lcn2 bound to Ent induces release of IL-8 from cultured respiratory cells. As a countermeasure, pathogens of the Enterobacteriaceae family such as Klebsiella pneumoniae produce additional siderophores such as yersiniabactin (Ybt) and contain the iroA locus encoding an Ent glycosylase that prevents Lcn2 binding. Whereas the ability of Lcn2 to sequester iron is well described, the ability of Lcn2 to induce inflammation during infection is unknown. To study each potential effect of Lcn2 on colonization, we exploited K. pneumoniae mutants that are predicted to be susceptible to Lcn2-mediated iron sequestration (iroA ybtS mutant) or inflammation (iroA mutant), or to not interact with Lcn2 (entB mutant). During murine nasal colonization, the iroA ybtS double mutant was inhibited in an Lcn2-dependent manner, indicating that the iroA locus protects against Lcn2-mediated growth inhibition. Since the iroA single mutant was not inhibited, production of Ybt circumvents the iron sequestration effect of Lcn2 binding to Ent. However, colonization with the iroA mutant induced an increased influx of neutrophils compared to the entB mutant. This enhanced neutrophil response to Ent-producing K. pneumoniae was Lcn2-dependent. These findings suggest that Lcn2 has both pro-inflammatory and iron-sequestering effects along the respiratory mucosa in response to bacterial Ent. Therefore, Lcn2 may represent a novel mechanism of sensing microbial metabolism to modulate the host response appropriately

Age-Related Differences In Plasma Theophylline Levels

WOS: A1994NV22900007PubMed ID: 7957450Because of its special pharmacokinetic properties, plasma levels of theophylline show significant differences between individuals and also its therapeutic index is very low. So, plasma theophylline concentration measurements are essential for an effective and safe treatment. In the present study, age related differences in plasma theophylline levels were evaluated in patients from different age groups. Patients were divided randomly into two groups. Group I included patients under the age of 50 years, group II included patients over 50 years of age. Plasma theophylline levels were measured before and 3, 7, 12 and 19 h after a single dose given orally. The results show that 3, 7 and 19 h post dose, levels of theophylline were significantly higher in group II than in group I (P < 0.001)

The importance of prolactin in acute rheumatic fever

Prolactin is an important hormone of the endocrine system. In recent studies, it has been shown that this hormone is related to the immune system and connective tissue disease. Acute rheumatic fever (ARF) is an immunologic disease in which connective tissue is also attacked. In this serie, we investigated the impact of prolactin on ARF. For this purpose, we detected serum levels of prolactin in patients before and after treatment. As a result we found that prolactin does not show any significant changes in the active period of ARF (P > 0.05)