Metabolic and immunological consequences of infection

Fever

Body temperature is controlled by the thermoregulatory centre in the anterior hypothalamus in the floor of the third ventricle. Gram-negative bacteria contain lipopolysaccharide (LPS) and peptidoglycan, which is also a component of Gram-positive bacterial cell walls. Toll-like receptors (TLR, p. 202) on monocytes and dendritic cells recognize these lipopolysaccharides and generate signals leading to formation of inflammatory cytokines, e.g. IL-1, -6, -12, TNF-α and many others. These cytokines act on the thermoregulatory centre by increasing prostaglandin (PGE2) synthesis. The antipyretic effect of salicylates is brought about, at least in part, through its inhibitory effects on prostaglandin synthase.

Fever production has a positive effect on the course of infection. However, for every 1°C rise in temperature, there is a 13% increase in resting metabolic rate and oxygen consumption. Fever therefore leads to increased energy requirements at a time when anorexia leads to decreased food intake. The normal compensatory mechanisms in starvation (e.g. mobilization of fat stores) are inhibited in acute infections. This leads to an increase in skeletal muscle breakdown, releasing amino acids, which, via gluconeogenesis, are used to provide energy.

Tumour necrosis factor (TNF)

TNF-α is released from a variety of phagocytic cells (macrophages/monocytes) and TNF-β from non-phagocytic cells (lymphocytes, natural killer cells) in response to infections (bacterial endotoxin) and inflammatory stimuli. TNF itself then stimulates the release of a cascade of other mediators involved in inflammation and tissue remodelling, such as interleukins (IL-1 and IL-6), prostaglandins, leukotrienes and corticotropin. TNF is therefore responsible for many of the effects of an infection.

The biological behaviour of the pathogen and the consequent host response are responsible for the clinical expression of disease that often allows clinical recognition. The incubation period following exposure can be helpful (e.g. chickenpox 14-21 days). The site and distribution of a rash may be diagnostic (e.g. shingles) while symptoms of cough, sputum and pleuritic pain point to lobar pneumonia. Fever and meningismus characterize classical meningitis. Infection may remain localized or become disseminated and give rise to the sepsis syndrome and disturbances of protein metabolism and acid-base balance. Many infections are self-limiting, and immune and non-immune host defence mechanisms will eventually clear the pathogens. This is generally followed by tissue repair, which may result in complete resolution or leave residual damage.