What causes a fever by acting directly on the hypothalamus?

A fever is primarily caused by the action of endogenous pyrogens, which are substances produced by the body itself, specifically in response to infection or inflammation. These endogenous pyrogens, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), are released by immune cells like macrophages and monocytes. They act directly on the hypothalamus, the brain region responsible for regulating body temperature.

When endogenous pyrogens are released into the circulation, they stimulate the hypothalamus to increase the body's temperature set point. This results in mechanisms that promote heat production (such as increased muscle tone and shivering) and decreased heat loss (through vasoconstriction) in order to raise the overall body temperature, leading to the clinical manifestation of a fever.

Understanding this process highlights the central role of endogenous pyrogens in the regulatory response to infection and emphasizes the body's innate mechanisms for fighting pathogens.