Biphasic fever: what triggers the second temperature rise?

Area of Science:

• Physiology
• Immunology
• Neuroscience

Background:

• Fever is a common response to infection, often characterized by biphasic body temperature (Tb) rises after lipopolysaccharide (LPS) administration.
• The precise mechanism initiating the second Tb rise in biphasic LPS fever remains poorly understood.
• Previous hypotheses suggested the second fever peak might be a consequence of the elevated Tb during the first phase.

Purpose of the Study:

• To investigate the hypothesis that the second Tb rise in biphasic LPS fever is initiated as a direct result of the elevated Tb from the first febrile phase.
• To differentiate between the direct effect of elevated Tb and other potential mechanisms for the second fever peak.

Main Methods:

• Experiments were conducted in conscious guinea pigs with implanted thermodes, catheters, and thermocouples.
• Intraperitoneal cooling (IPC) was applied during either the first or second phase of biphasic LPS fever, or during monophasic LPS fever, to modulate Tb.
• Control groups received LPS without IPC, or IPC under afebrile conditions.

Main Results:

• IPC initiated during the first phase of biphasic LPS fever completely blocked this initial Tb rise.
• A subsequent Tb rise occurred, but analysis, including Tb restoration after IPC, ruled out a delayed first phase.
• IPC applied during the second phase of biphasic fever or during monophasic fever did not reveal an overshoot, further supporting the independence of the second phase.

Conclusions:

• The second body temperature rise in biphasic LPS fever is not initiated by the elevated Tb of the first febrile phase.
• The underlying cause for the second peak in LPS-induced biphasic fever remains undetermined and requires further investigation.