In his fascinating article, Mackowiak [1] proposes an attractive hypothesis for the continuing debate on the teleologic question of fever as a friend or an enemy. This hypothesis reconciles the results of experimental and clinical studies that show fever both as friend and foe. However, it is important to note that in some of the studies attributing organic damage to fever, the damage is actually caused by hyperthermia, a well-known mechanism of injury [2]. In hyperthermia, no defenses against aggression are activated, liberation of cytokines is not implicated, and prostaglandin synthesis is not involved. Instead, a dysfunction of thermoregulatory mechanisms leads to a temperature sometimes sufficient to cause thermal damage. Although fever is a manifestation of a functional thermoregulatory system, hyperthermia is characteristic of a disarranged one. Examples of hyperthermia are heat stroke, anhydrosis, occlusive clothes, hypothalamic injuries, and malignant hyperthermia. A difference also exists experimentally between induced hyperthermia and induced fever; the former is achieved by warming and the latter by pyrogen injection.

Although I agree with Dr. Mackowiak's unifying hypothesis, some of the apparent contradictions concerning the organic effects of fever can be caused by a lack of distinction between fever and hyperthermia. It is clear that the latter must be suppressed, whereas febrile response can contribute to face aggression.