BIPHASIC FEVERS OFTEN CONSIST OF MORE THAN 2 PHASES

This paper disproves the common belief that all doses of lipopolysacch aride (LPS) that are commonly referred to as biphasic fever inducing ( greater than or equal to 2 mu g/kg) cause truly biphasic responses. A catheter was implanted into the right jugular vein of several strains of adult male rats, and the animals were habituated to the experimenta l conditions. At an ambient temperature of 30.0 degrees C, loosely res trained animals were injected with a 10 mu g/kg dose of LPS (various p reparations), and their colonic (T-c) and tail skin temperatures were monitored (from greater than or equal to 1 h before to greater than or equal to 7 h after the injection). The results are presented as time graphs and phase-plane plots; in the latter case the rate of change of T-c is plotted against T-c. In experiment 1 the intravenous injection of LPS (from Escherichia coli 0111:B4, phenol extract) into the rats (Bkl:Wistar) induced a triphasic febrile response, as is obvious from time graphs of T-c (3 peaks), time graphs of effector activity (3 wave s of tail skin vasoconstriction), and phase-plane plots (3 complete lo ops); the injection of saline (control) induced no T-c changes. We ana lyzed whether the triphasic pattern was due to some peculiarities of t he experimental design, i.e., the pyrogen preparation used (experiment 2) or the rat strain tested (experiment 3) or whether this pattern re flects a more general law. In experiment 2 we used the same (phenol) p reparation of different LPS (from Shigella flexneri 1A and Salmonella typhosa) and a different preparation (TCA extract) of the same LPS (E. coli). Regardless of the LPS used, rats of the Bkl:Wistar strain resp onded to the 10 mu g/kg dose with the triphasic fever. In experiment 3 , rats of other strains [Bkl: Sprague-Dawley and Sim:(LE)fBR(Black-hoo ded)] were tested. Again, all animals responded to the 10 mu g/kg dose off. coli LPS (phenol extract) with the triphasic fever. Because all fevers caused by four different LPS preparations in three rat strains were triphasic, the triphasic pattern is likely to constitute an intri nsic characteristic of the febrile response.