TUMOR-NECROSIS-FACTOR AND INTERFERON ACTIVITY IN THE CIRCULATION OF CALVES AFTER REPEATED INJECTION OF LOW-DOSES OF LIPOPOLYSACCHARIDE

The effect of two intravenous (iv) injections of low doses of lipopoly saccharide (LPS)(0.1 mu g/kg of body weight) administered at 7-day int ervals on the systemic release of tumor necrosis factor (TNF) and inte rferon (IFN), on the rectal temperature, breathing and heart rate, and on packed cell volume (PCV), plasma glucose concentration, white bloo d cell (WBC) counts in 3-week-old calves, was estimated. The first inj ection of LPS caused a significant increase in breathing and heart rat e, rectal temperature, prolonged hypoglycemia and leukopenia, but no s ignificant changes in PCV were observed. TNF and IFN activity peaked a t 2 h after LPS injection and disappeared from circulation by 4 h and 5 h, respectively. After the second injection of LPS, the reaction of calves was similar to that observed after the first injection, however , the breathing rate and TNF systemic production were significantly re duced. The results obtained indicate that a low dose of LPS leads to t he development of 'late' tolerance manifested by hyporeactivity to TNF production but with maintained responsivity to IFN production, pyroge nic, hypoglycemic and leukemic response to the second injection of LPS . In conclusion, these results demonstrate that the tolerance response is not universal to all hematologic and immunologic parameters, and t hat the response needs to be evaluated with respect to the specific va riable. (C) 1998 Published by Elsevier Science B.V.