pyrogens

Pyrogens are substances that induce fever, a regulated rise in body temperature. They include exogenous microbial products such as endotoxins, particularly lipopolysaccharide (LPS) from Gram-negative bacteria, and various bacterial exotoxins. They also comprise endogenous pyrogens, primarily cytokines released by activated immune cells, notably interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α).

The fever response is triggered when pyrogens influence the hypothalamus, the brain’s temperature-regulating center. Exogenous pyrogens stimulate immune cells to produce endogenous pyrogens, which in turn induce cyclooxygenase-2–mediated synthesis of prostaglandin E2 in the hypothalamus. Prostaglandin E2 raises the set-point for body temperature, producing fever.

Classification and sources can be described as exogenous pyrogens (microbial components), endogenous pyrogens (cytokines and mediators from immune cells), and pyrogenic substances from non-microbial sources. Fever may arise from infection, inflammation, or tissue injury and can be an adaptive response that helps host defense, though it may be harmful in certain populations or clinical situations.

In clinical and pharmaceutical contexts, pyrogens are a concern because they can contaminate injectable drugs and medical devices. Endotoxins are detected using the Limulus amebocyte lysate (LAL) assay, while newer approaches such as the monocyte activation test (MAT) assess broader pyrogenicity. Management of fever typically involves supportive care and, when appropriate, antipyretics such as NSAIDs or acetaminophen.

The term pyrogen derives from Greek roots meaning fever-producing.