Figure 1: Fever curves during febrile and afebrile conditions

The broken line represents the normal diurnal temperature variation in an afebrile person,  peaking in the late afternoon and reaching a nadir in the early morning. The solid line is the temperature curve during a febrile illness. The diurnal variation is maintained but at a higher set point during infection. The temperature rises because of an increase in the hypothalamic set point (rising vertical dotted arrow) to a new higher set point (40º C). Heat is generated by shivering causing chills (C). Heat is lost by sweating (S) when the set point is lowered (falling vertical arrow) toward the “normal” set point. The solid arrow represents administration of an antipyretic. This artificially lowers the set point to a greater extent than would be expected during the normal diurnal variation of an infection causing a marked fall in temperature. The patient experiences a “drenching” night sweat.

Used with permission by Marcel Dekker Inc in Medical Management of Infectious Diseases, Ed C Grace, 2003.

Figure 2: Sagittal view of a mammalian brain.

This shows the position of the anterior hypothalamus, organum vasculosum lamina terminalis (OVLT), reticular formation (RF) and spinothalamic tract (STt) and the preoptic and septal nuclei of the hypothalamus.

 Used with permission from Mackowiak PA, Concepts of Fever. Arch Intern Med 1998;158:1870-1881.

Figure 3: Fever, immunity and the inflammatory response

Exogenous pyrogen stimulates cytokine (endogenous pyrogen) release. IL-1, IL-6, TNF and INF reset the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT). The body temperature is raised. Endogenous pyrogen also triggers immunologic, inflammatory and metabolic responses that in turn help control the exogenous pyrogen (dashed lines). Elevation in body temperature also improves the immunologic and inflammatory responses (dotted lines).

WBC = white blood cell, IL-1=interleukin-1, IL-6 = interleukin-6, TNF = tumor necrosis factor, INF = interferon, NK = Natural Killer, Zn = zinc, Fe = iron, Cu = copper

Used with permission by Marcel Dekker Inc in Medical Management of Infectious Diseases, Ed C Grace, 2003.

Figure 4: Prostaglandin E₂ production

Prostaglandin E₂ is synthesized from membrane bound phospholipid by phospholipase A₂ and cyclooxygenase (COX). Corticosteroids inhibit phospholipase A₂ while aspirin and non-steroidal anti-inflammatory drugs inhibit COX. Metabolites of acetaminophen can inhibit COX isoenzymes.

IL-1 = interleukin –1, TNF = tumor necrosis factor, IL-6 = interleukin-6, IFN = interferons, ASA = acetylsalicylic acid, NSAIDS = non-steroid anti-inflammatory drugs

Used with permission by Marcel Dekker Inc in Medical Management of Infectious Diseases, Ed C Grace, 2003.

Table 1: Direct and indirect effects of Interleukin - 1

Table 2: Benefits of fever

Table 3: Hyperthermia