Submandibular glands: novel structures participating in thermoregulatory responses

Since submandibular glands participate in the regulation of cardiovascular and immunological responses to bacterial endotoxin, we examined their role as modulators of endotoxin-induced fever. Core body temperatures were measured by telemetry in rats that had either a sham operation or a sialadenectomy 1 week previously and that were maintained at 23-24 degrees C. The sialadenectomized rats showed a circadian variation in body temperature similar to sham-operated rats, although their daytime body temperature was 0.24 +/- 0.01 degree C lower. The fever elicited by intraperitoneal injection of Escherichia coli endotoxin was biphasic, with an initial phase occurring between 2 and 3 h, and a broader second phase peaking between 4 and 8 h after endotoxin injection. The initial fever was similar in the two groups of rats, but the second phase of fever was significantly higher by 0.28 +/- 0.09 and 0.26 +/- 0.07 degree C in sialadenectomized rats receiving 50 or 150 micrograms/kg of endotoxin, respectively. Intravenous treatment with a novel peptide, submandibular gland peptide-T (SGP-T; 100 micrograms/kg), 30 min before endotoxin injection did not affect the early fever response, but significantly suppressed by 0.37 +/- 0.10 degrees C the late-phase fever provoked by 150 micrograms/kg of endotoxin. These results suggest that the submandibular glands modulate thermogenic responses to inflammatory stimuli possibly through the endocrine release of hormones, such as SGP-T.