poundmed.com

It is difficult to imagine a time when humans weren’t preoccupied with the mysteries of fever and its treatment. Efforts to probe the pathophysiology of the febrile response are evident as early as 2,500 years ago, when the Sumerians used a pictogram of a aming brazier to symbolize fever. This earliest known effort to conceptualize mechanisms responsible for fever evolved slowly through the humoral theory of the Hippocratic era, the demonic-possession explana­tion of the Middle Ages, the friction and fermen­tation theories of Renaissance iatrophysicists and iatrochemists, to the pyrogen-mediated schema we now accept as valid today.

Treatment of fever, too, has a long history. Most likely, external cooling has always been used by humans to lower the temperature of febrile patients. Antipyretic drugs, surprisingly, may have been in use almost as long. The ancient Assyrians, Egyptians, and Greeks all apparently knew of and exploited the antipyretic property of extracts of willow bark.2 Observations of similar practices among aboriginal peoples suggest that antipyretic drug therapy might antedate even these ancient societies.In spite of many millennia of deep interest in fever and over a century of intensive, modern in­vestigation, it is astounding how little progress has been made in answering some of the most funda­mental questions about the response. We do not, for example, even know how best to monitor “body temperature.” This is because the body actually is composed of a pastiche of many different tempera­tures, which vary according to anatomic site, time of day, level of activity, gender, and a host of other factors only partially understood. Thus, there is really no such thing as “body temperature,” only temperatures of various body parts that correlate but roughly one to another, and each has its own relative merit as a metric of health status.Then there is the pyrogen-mediated fever path­way in which exogenous pyrogens induce phago­cytic leukocytes to release pyrogenic cytokines that stimulate production of prostaglandin E₂ in the pre-optic area of the anterior hypothalamus; these pyrogens, in so doing, turn up the body’s internal thermostat.3 Although this hypothetical pathway is simple, logical, and consistent with much experimental data, not all thermophysiolo­gists agree that the anterior hypothalamus houses an internal thermostat. Moreover, even if the py­rogen-pathway hypothesis is valid, it explains only why core temperature rises during fever. It tells us nothing about why it levels off rather than contin­ues to rise, or why it falls and then rises again in circadian fashion even during a condition such as bacterial endocarditis, in which levels of circulat­ing exogenous pyrogens (bacteria) remain virtu­ally constant throughout the day and night.Finally, there is the matter of antipyretic ther­apy. After several millennia of experience and in spite of an astonishing array of antipyretic drugs in use today, we have yet to determine whether fever, per se, is ever noxious or the measures we use to suppress it do more good than harm. Aside from the obvious problems of aspirin-induced Reye’s syndrome in children, acetaminophen liver toxic­ity, cooling blanket-induced cold pressor respons­es, nonsteroidal anti-in?ammatory drug-related cardiac events, and the like, there is mounting evidence that antipyretic drugs prolong the course of at least some viral infections—notably, rhino­virus,4 measles,5 varicella,6 and in?uenza A7 in­fections—suggesting that the symptomatic relief afforded by antipyretic drugs in such infections is not without cost.In 1960, Bennett and Nicastri8 wrote that fever is “a sub­ject considered less in the laboratory of the investigator and more in the realm of the turner of neat phrases and composer of aphorisms.” The challenge implicit in their words is no less relevant today than it was almost 50 years ago.

Popularity: 6% [?]