Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages.

Hyperbaric oxygen (HBO) is 100% oxygen administered at elevated atmospheric pressure to patients with inflammatory diseases. We developed an in vitro model to investigate the effects of HBO on stimulus-induced proinflammatory cytokine transcription and translation. Human blood-derived monocyte-macrophages were stimulated before being transferred to an HBO chamber where they were incubated at 97.9% O2, 2.1% CO2, 2.4 atmospheres absolute, 37 degrees C. Controls were maintained in the same warm room at normoxia at sea level, hyperoxia or increased pressure alone. A 90-min HBO exposure inhibited IL-1beta synthesized in response to lipopolysaccharide by 23%, lipid A by 45%, phytohaemagglutinin A (PHA) by 68%, and tumour necrosis factor (TNF)-alpha by 27%. HBO suppressed lipopolysaccharide-, lipid A- and PHA-induced TNF-alpha by 29%, 31% and 62%, respectively. HBO transiently reduced PHA-induced steady state IL-1beta mRNA levels. Hyperoxia alone and pressure alone did not affect cytokine production. The immunosuppressive effect of HBO was no longer evident in monocyte-macrophages exposed to HBO for more than 3 h. Interestingly, cells exposed to HBO for 12 h synthesized more IL-1beta than cells cultured under control conditions. In summary, HBO exposure transiently suppresses stimulus-induced proinflammatory cytokine production and steady state RNA levels.

Hyperbaric oxygen enhances apoptosis in hematopoietic cells.

Hyperbaric oxygen (HBO) is 100% oxygen administered at elevated atmospheric pressure. In this study, we examined the effect of HBO on hematopoietic cell apoptosis. Cells exposed to HBO were incubated in a chamber containing 97.9% O(2) and 2.1% CO(2) at 2.4 atmospheres absolute (ATA). HBO enhanced spontaneous HL-60 cell apoptosis in a time-dependent manner; a 12 h exposure increased apoptosis by 42%. Exposing these cells to hyperoxia at standard atmospheric pressure (95% O(2), 5% CO(2) at 1 ATA) or increased pressure alone (8.75% O(2), 2.1% CO(2) at 2.4 ATA) had minimal effect on apoptosis. HBO also enhanced stimulus-induced apoptosis. HL-60 cells stimulated to die using gamma radiation underwent 33% more apoptosis than cells exposed to radiation alone. HBO enhanced melphalan, camptothecin, and chlorambucil-induced apoptosis by 22%, 13%, and 8%, respectively. Jurkat cells stimulated to die with anti-Fas antibody underwent 44% more apoptosis when exposed to HBO. Spontaneous apoptosis was increased by 15% in HBO-exposed murine thymocytes. HBO's effect on apoptosis did not require new protein synthesis. As expected, HBO exposure increased the intracellular concentration of H(2)O(2). Incubating HL-60 cells in the presence of dehydroascorbic acid partially abrogated HBO-induced increases in intracellular H(2)O(2) and apoptosis. In summary, HBO enhances spontaneous and stimulus-induced apoptosis in hematopoietic cells, at least in part, by enhancing the intracellular accumulation of H(2)O(2).

Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans.

This study examines the effects of hyperoxia, increased atmospheric pressure, and hyperbaric oxygen on cytokine synthesis. Five healthy volunteers were exposed to 90 min of room air, 100% oxygen, 10.5% oxygen at 2 atm abs, or 100% oxygen at 2 atm abs (HBO2). All subjects were blinded and randomly exposed to each of the 4 conditions. Immediately before entering the chamber, immediately after exposure, and 3 and 24 h later, blood was drawn and stimulated ex vivo with phorbol myristate acetate (PMA) and phytohemagglutinin A (PHA). Since lymphocytes are the primary source of PMA/PHA-induced interferon-gamma (IFN-gamma), these results were expressed as IFN-gamma production per 10(6) lymphocytes. Following the HBO2 exposure, PMA/PHA-stimulated lymphocytes released 51% less IFN-gamma than cells obtained before the exposure. This suppression persisted for 24 h following HBO2 (P < 0.05). Surprisingly, increased atmospheric pressure alone also inhibited IFN-gamma secretion (P < 0.05). Room air and hyperoxia alone had no significant effect upon IFN-gamma release. HBO2's anti-inflammatory effect may, in part, be due to inhibition of IFN-gamma release.

Reliability of the Group for Advancement of Psychiatry Diagnostic Categories in Child Psychiatry.

A total of 403 multiple diagnoses were independently assigned to 41 patient protocols by 73 psychiatrists, psychologists, and social workers to determine the levels of interrater reliability of the Group for the Advancement of Psychiatry (GAP) diagnostic categories. With the exception of the psychotic disorders category, these diagnostic categories were found to have low levels of interdiagnostician reliability. Differences in the reliabilities across disciplines and levels of training were found. It is noted, however, that neither years of experience, kind of training, nor direct contact with the patient can be regarded as a substitute for improvements in the classification system itself. The importance of a reliable classification system for child psychiatry is emphasized and suggestions for improvements in the present GAP system are made.