Semantics, Inflammation, Cytokines and Common Sense

Semantic evaluation of some of the terms we regularly employ—inflammation, anti-inflammatory, pro-inflammatory, anti-inflammatory drugs, cytokines, homeostasis and stress—raises concerns about their precise meanings and about their mechanistic implications. Semantic imprecision may have undesirable conceptual consequences.     

Biochemical aspects of inflammation

This review considers biochemical aspects of inflammation. The international literature until December 2006 has been analyzed, with the principal attention paid to the most dynamic problems: enzymology of inflammation, its regulation by hormones and signal transducers, and negative feedbacks, which underlie intensive current studies on pathogenesis, diagnostics, and therapy of inflammation. Such achievements as discoveries of defensins, toll-like receptors, interconnections of inflammation and iron metabolism, the roles of oxidative stress and antioxidant defense, lipoxins, inflammatory components of "non-inflammatory" diseases, and action mechanisms of effective drugs are discussed.     

The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection

Aging is accompanied by the development of low‐grade systemic inflammation, termed ‘inflammaging’, characterized by raised serum C‐reactive protein (CRP) and pro‐inflammatory cytokines. Importantly, inflammaging is implicated in the pathogenesis of several of the major age‐related diseases including cardiovascular disease, type 2 diabetes, and dementia and is associated with increased mortality. The incidence of infection with the persistent herpes virus cytomegalovirus (CMV) also increases with age. Cross‐sectional studies have proposed CMV infection as a significant driver of inflammaging, but a definitive case for CMV as a causative agent in inflammaging has not yet been made. We studied longitudinally 249 subjects (153 men, 96 women) who participated in the Hertfordshire Ageing Study at baseline (1993/5, mean age 67·5 years) and at 10 year follow‐up. At both times, anthropometric measurements were made and subjects provided blood samples for analysis of inflammatory status and CMV seropositivity. In the cohort as a whole, serum CRP (P < 0·02) and pro‐inflammatory cytokines TNFα (P < 0·001) and IL‐6 (P < 0·001) were increased between baseline and follow‐up sampling whereas levels of the anti‐inflammatory cytokine IL‐10 were decreased (P < 0·001). These changes to cytokine status over time occurred equally in the 60% of subjects who were seropositive for CMV at baseline and follow‐up, the 8% who were CMV negative at baseline but who became CMV positive by the 10 year follow‐up, and also in the 32% who were CMV seronegative throughout. We conclude that CMV infection is not a primary causative factor in the age‐related increase in systemic inflammation.     

Starch in plasterboard sustains Streptomyces californicus growth and bioactivity of spores

AIMS: The effects of plasterboard composition on Streptomyces californicus growth and bioactivity of spores were studied. METHODS AND RESULTS: Streptomyces californicus was grown on 13 modified plasterboards under saturated humidity conditions. The total content of fatty acid methyl esters was used for quantifying S. californicus biomass, while the spore-induced cytotoxicity and production of nitric oxide (NO), tumour necrosis factor-alpha, and interleukine-6 (IL-6) in mouse macrophages was used to assess the bioactivity of spores. Removal of starch completely from the plasterboard or only from the core reduced significantly the biomass production and the biological activity of spores in comparison with reference board. The biocide added into the core or on the liner decreased the growth markedly and inhibited the sporulation totally. The biomass production correlated positively with the spore number, cytotoxicity, and production of NO and IL-6. CONCLUSIONS: Streptomyces californicus grew under nutrient limitation on all studied plasterboards. The starch is the major factor enabling S. californicus to grow and to produce biologically active metabolites on plasterboard. SIGNIFICANCE AND IMPACT OF THE STUDY: The composition of building material has an impact on microbial growth and bioactivity of spores which may be involved in complex mechanisms leading to respiratory symptoms in the occupants in moisture damaged buildings.     

Characterization of bovine FAS-associated death domain gene

The FAS-associated death domain (FADD) protein is an adapter/signaling molecule that has been shown to function in human cells to promote apoptosis and to inhibit NF-kappaB activation. Because of the critical role that apoptosis and NF-kappaB play in a variety of disease states, we mapped the bovine FADD gene, sequenced bovine FADD cDNA, and characterized its expression in endothelial cells (EC). Sequencing of bovine FADD revealed approximately 65 and 58% amino acid sequence identity to its human and murine homologues, respectively. Bovine FADD was mapped to chromosome 29 by radiation hybrid mapping. In addition, the functionality of bovine FADD was studied. Expression of a bovine FADD dominant-negative construct blocked bacterial lipopolysaccharide (LPS)- and TNF-alpha-induced apoptosis in bovine EC consistent with previous studies of human FADD. In contrast to human FADD, elevated expression of bovine FADD had no effect on LPS- or TNF-alpha-induced upregulation of NF-kappaB-dependent gene products as assayed by E-selectin expression. Thus, while the role of FADD in mediating apoptosis is conserved across species, its role in regulating NF-kappaB-dependent gene expression is not.