pyrogenssubstances

Pyrogens, or pyrogenic substances, are agents that induce fever by acting on the body's thermoregulatory center in the hypothalamus. They can be categorized as exogenous, derived from pathogens, or endogenous, produced by the host immune system in response to infection or inflammation.

Common exogenous pyrogens include bacterial endotoxins such as lipopolysaccharide (LPS) from Gram-negative bacteria, as well as other microbial components like lipopeptidoglycan. Endogenous pyrogens include cytokines such as interleukin-1 beta (IL-1β), interleukin-6, and tumor necrosis factor-alpha (TNF-α). These substances act as signals of infection and help coordinate immune responses.

Mechanism: these pyrogens stimulate the production of prostaglandin E2 in the hypothalamus, which raises the body's thermoregulatory set-point. The result is fever, accompanied by systemic inflammatory responses that can influence leukocyte activity and metabolic processes.

In medicine and pharmacology, pyrogens are important safety concerns because fever and inflammatory reactions can be dangerous for patients. Regulatory guidelines require testing of injectable products for pyrogens. Traditional tests include the rabbit pyrogen test, which measures fever response in rabbits, and the limulus amebocyte lysate (LAL) test, which detects endotoxins in many products. In vitro alternatives, such as the Monocyte Activation Test (MAT), use human immune cells to detect a broader range of pyrogens and are increasingly adopted.

Not all pyrogens are endotoxins; non-endotoxin pyrogens may escape LAL testing, underscoring the need for comprehensive safety assessments. Pyrogenicity is evaluated per dose, with limits defined in pharmacopeias and regulatory frameworks to ensure product safety and patient protection.