STUDIES ON THE MECHANISM OF FEVER AFTER INTRAVENOUS ADMINISTRATION OFENDOTOXIN

Background: The sequential events in fever production after intravenou s administration of lipopolysaccharide (LPS) remain unsettled and cont roversial. Vessels of the organum vasculosum laminae terminalis (OVLT) lack the tight junctions of the blood-brain barrier and allow substan ces of high molecular weight to enter the interstitium but not the neu ropil. The present studies investigate the hypothesis that the OVLT is needed for fever production after intravenous administration of LPS i n the rat. Methods: Electrolytic lesions were produced in the OVLT of rats. After recovery, left carotid and right atrial catheters were ins erted, and 24 hours later calorimetry was performed. Blood was drawn f or baseline assay for cytokines and LPS after which LPS was given intr avenously, with studies continued for 5 hours, and additional blood sa mples were drawn at 90 and 300 minutes. Results: The maximal increment in rectal temperature for the sham lesion LPS group (1.25 +/- 0.44 de grees C) was significantly greater than for the sham-saline (-0.05 +/- 0.46 degrees C) and the lesion-LPS groups (0.35 +/- 0.45 degrees C) f or minutes 120 to 300. Ninety minutes after LPS administration, serum levels of interleukin (IL)-6, tumor necrosis factor-alpha, and LPS wer e significantly elevated (p < 0.0001) above baseline for the sham-LPS and lesion-LPS groups, IL-1 beta serum levels remained below detection levels. Conclusion: Large lesions of the OVLT prevent and/or attenuat e fever due to LPS even though tumor necrosis factor-alpha and IL-6 ar e greatly increased in serum, IL-1 beta does not seem to be an endogen ous humoral mediator in this model.