Comparison of the Methods for Determining Pyrogenically Modified Carbon Compounds

The soil organic matter (SOM) is searched for the biomarkers and specific features associated with the effect of wildfires by the case study of peat soil, Rheic Hemic Histosol (Lignic), in the south of the middle taiga of the Komi Republic. It is shown that fires considerably influence the peat organic matter. Pyrogenic activity is assessed according to the content of charcoal particles. SOM is examined using solid-state 13C-NMR spectroscopy to determine the concentrations of polycyclic aromatic hydrocarbons (PAHs) and benzene polycarboxylic acids (BPCAs). The used methods allow for diagnosing the effects of wildfires on the SOM composition. In the horizons with the signs of pyrogenesis, the share of carbon represented by aromatic fragments increases as well as the PAH concentration, mainly at the expense of naphthalene, phenanthrene, and chrysene. The carbon stock of pyrogenically modified compounds, amounting to 4.4 kg/m2, is for the first time assessed in the European north based on the BPCA content. The characteristics of pyrogenically changed organic compounds and their fragments obtained by different methods correlate well: the Pearson coefficient for the correlation of the carbon content in aromatic compounds (Caryl) with total BPCA content is R = 0.84 (p < 0.05) and with individual BPCAs, R = 0.81–0.90 (p < 0.05).

Pyrogenicity of human adenoviruses

High doses (>1·56×107 p.f.u.) of purified preparations of human adenovirus types 3, 5 and 8 exhibited definite pyrogenic activity when injected intravenously into rabbits. Complete pyrogenic tolerance was obtained not only with homologous types but also with heterologous types of adenovirus. No pyrogenic cross-tolerance was observed between each of these three adenovirus types and paramyxovirus pyrogen or bacterial lipopolysaccharide. Adenovirus pyrogenicity was retained after UV-inactivation, whereas it was inactivated by heating at 56 °C for 30 min. Adenovirus pyrogenicity was not neutralized by mixing with homologous type-specific antiserum but non-pyrogenic doses (107 p.f.u.) of adenovirus types 3, 5 and 8 became highly pyrogenic in the presence of type-specific antibodies at the optimal virus:antibody ratio. This enhanced pyrogenicity depended upon the virus–antibody complex. From these results, it is probable that the pyrogenic activity of the virus–antibody complex, rather than the pyrogenic activity of the virions, is the main contributor to fever in adenovirus infection under actual physiological conditions.

Blood-borne, albumin-bound prostaglandin E2 may be involved in fever

Although the involvement of blood-borne PGE2 in fever has been hypothesized by several authors and has substantial experimental support, the current literature often rejects this hypothesis because several attempts to induce fever by a peripheral PGE2 failed. However, it is usually ignored that the amphipathic molecules of PGE2 are readily self-associating and that such an aggregation could have prevented the peripherally administered PGE2 (free form) from expressing its pyrogenic activity, thus leading to false negative results. To ensure disaggregation of PGE2, we prepared its complex within a carrier protein, human serum albumin (HSA). HSA was purified with activated charcoal and polymixin B-polyacrylamide gel and incubated with PGE2 for 1 h at 37°C. Adult Chinchilla rabbits were injected intravenously with PGE2-HSA complex in either the higher (75 μg/kg PGE2:30 mg/kg HSA) or the lower (15 μg/kg:6 mg/kg) dose, and the rectal temperature (Tr) was measured. In the controls, either the ligand alone or the carrier alone was administered. At the higher dose, neither free PGE2 nor albumin alone was pyrogenic, whereas the PGE2-HSA complex produced a fever characterized by a short latency (<10 min) and a maximal Tr rise of 0.7 ± 0.2°C. At the lower dose, none of the substances affected the Tr. This study demonstrates a marked pyrogenic activity of the intravenous PGE2-HSA, but not of the free PGE2. Administration of a preformed complex may be more physiologically relevant than administration of the free ligand because of the ligand’s disaggregation, protection from enzymatic degradation, and facilitated delivery to targets. Our study supports the hypothesis that peripheral PGE2 is involved in fever genesis.

Individual differences in response to LPS and psychological stress in aged rats

Old rats may show blunted fever or hypothermia after injection of lipopolysaccharide (LPS), a fever-producing agent, and have a reduced body temperature (Tb) rise in response to psychological stress. These results may partly be a consequence of aging per se, partly a sex difference, and partly an effect of differences in types and doses of pyrogen. Here we tested age and gender differences in Tb responses to 30-min exposure to a novel environment and to injection of several doses of LPS. There were age-related reductions in novelty-induced hyperthermia, and some old rats even became hypothermic. Sensitivity to the pyrogenic activity of LPS and to the toxic effects of endotoxin (manifested by hypothermia) both increased in aged female rats. A major finding was that there were no correlations between age-related changes in Tb in response to novelty and to LPS injection. Tb responses in aged rats were variable; in each situation, there were old rats whose Tb rose as high as did younger ones. We did not observe significant gender differences in response either to novelty or to LPS in young or old rats.

Interleukin-1 receptor antagonist inhibits endotoxin fever and systemic interleukin-6 induction in the rat

Although a number of studies indicate that the pyrogenic activity of lipopolysaccharide (LPS) and/or interleukin (IL)-1 is mediated via induction of IL-6, this has been questioned by recent evidence demonstrating a dissociation between fever and circulating IL-6. The present study reexamines this relationship by use of human recombinant interleukin-1 receptor antagonist (IL-1ra). Injection of LPS (100 micrograms/kg ip) into rats induced fever (2.0 degrees C) that was significantly inhibited (P < 0.05) when IL-1ra (16 mg/kg ip) was given 1 and 2 h after LPS. The rise in plasma IL-6 preceded the febrile response by 1-1.5 h and, although the concentrations of bioactive IL-6 in plasma and cerebrospinal fluid (CSF) were not reduced at 4 h, at 2 h plasma and CSF IL-6 bioactivity was inhibited by 80 and 70%, respectively, after a single injection of IL-1ra (16 mg/kg ip). Intracerebroventricular injection of IL-1ra (200 micrograms/rat) inhibited LPS fever but did not affect the plasma IL-6 bioactivity measured 2 or 4 h after intraperitoneal LPS. These data show that peripheral IL-1 plays a part in the induction of both fever and the rise in plasma IL-6 that precedes it, and that IL-1 within the brain is also important in the induction of fever by LPS.