Alterations in hepatic chromatin template availability during infection.

Abstract

Hepatic chromatin was isolated from rats at various times after inoculation with either live or heat-killed bacteria. The chromatin was assayed under conditions that allow determination of the DNA template available to support in vitro transcription. Both a fulminant Diplococcus pneumoniae and a milder Salmonella typhimurium infection produced time-related increases in hepatic chromatin template availability when compared to chromatin isolated from rats inoculated with heat-killed bacteria. Both timing and magnitude of increased template availability correlated with the severity of the infection. The earliest change observed was a 50 percent rise in availability noted 4 h after inoculation with D. pneumoniae. This preceded the onset of fever, as well as other known heaptic consequences of systemic infection. After 24 h of infection the maximum rise of 90 percent occurred. Similar changes developed during S. typhimurium infection, but were slower in onset and smaller in magnitude. Adrenalectomy prior to infection enhanced the severity of the disease but markedly blunted the increase in template availability. The data are consistent with the hypothesis that systemic infection regulates the hepatic metabolic response to infection through transcriptional control and that a permissive or stimulatory action of glucocorticoids is involved in the increases in template availability effected.