The effect of age and gender on the peripheral blood cell response to Escherichia Coli lipopolysaccharide (LPS) in Wistar rats (Rattus Norvegicus)

Thesis (Ph. D.)--University of Hawaii at Manoa, 1994.Includes bibliographical references (leaves 147-160).Microfiche.xvii, 160 leaves, bound ill. 29 cmEscherichia coli (E. coli) lipopolysaccharide (LPS) is the major component of mammalian gut bacterial flora. Inflammatory diseases of unknown etiology, e.g., rheumatoid arthritis, may be triggered by periodic transmural release of LPS from the gut into the peritoneal cavity. If so, an older animal should have a greater exposure history to LPS and, therefore, be hyper-responsive. Age and gender-related variation in peripheral blood cell responsiveness was determined in untreated rats (time zero). The acute (0-2 day) and long-term (3-24 day) response to an intraperitoneal injection of 0.5 mg/kg E. coli LPS was compared to control (sterile 0.9% saline) in young, middle-aged, and old male and female Wistar rats. In untreated rats, a number of parameters changed with age: older rats had increased white blood cell (WBC) chemiluminescence (CL) , time-to-peak CL, plasma protein concentration, and decreased WBC total count, and in vitro WBC mobility. Packed cell volume (PVC) increased in middle-age, but decreased in old rats. Saline-treated male rats had higher WBC counts, body weight, CL, and PVC when compared to age-matched, saline-treated, female rats. Acutely, LPS caused a hypothermia in all rats, which was more profound and prolonged in the old rats. Hypothermia was followed by fever, which was highest in the young rats. LPS also increased WBC counts and CL, and decreased time-to-peak WBC CL in all rats. WBC CL was greater in old and middle-aged rats during days 13-24 following LPS. Blood-free, homogenized, liver cell CL tripled in old age. These findings suggest that LPS was a pro-inflammatory stimulant, particularly in the middle-aged and old rats. Interestingly, this effect of LPS appears to eliminate many age and gender effects noted in the untreated animals. The observation that a single I.P. injection of LPS has no effect on WBC CL during the first three hours and increases CL during hours 3-48 in all but the old female group, and that the old female rats' WBC CL was depressed during the first 12 hours and enhanced at hour 48, may explain some of the conflicting observations made by others using shorter protocols