A 72-year-old woman is brought to the emergency department from a nursing facility due to fever, chills, and hypotension. The patient has a history of diabetes mellitus, ischemic stroke, and neurogenic bladder. She has an indwelling urinary catheter. Temperature is 38.8 C (102 F), blood pressure is 80/40 mm Hg, and pulse is 130/min. The patient is lethargic and disoriented. Her extremities are warm, and her breathing is rapid and shallow. Lungs are clear on auscultation and there are no heart murmurs. There is left costovertebral angle tenderness. The urine in her catheter appears cloudy. Her leukocyte count is elevated with left shift, and urinalysis shows pyuria and bacteruria. Which of the following chemical mediators is most responsible for this patient's current condition?
When observed in the setting of infection, the combination of hypotension, tachycardia, tachypnea, and markedly elevated or decreased body temperature is suggestive of septic shock. Early sepsis is characterized by peripheral vasodilation, a compensatory increase in cardiac output, and warm extremities.
Numerous cytokines are released in sepsis, resulting in widespread systemic inflammation. One of the most important mediators of sepsis is tumor necrosis factor-alpha (TNF-α), an acute-phase cytokine produced by activated macrophages. TNF-α stimulates systemic inflammation via recruitment of additional leukocytes (eg, neutrophils, macrophages) and increasing pro-inflammatory cytokine production. Other cytokines responsible for inducing the systemic inflammatory response in sepsis include IL-1 and IL-6.
(Choice A) IL-3 is a cytokine produced by activated T cells. It stimulates the growth and differentiation of stem cells in the bone marrow.
(Choice B) IL-4 is a cytokine produced by Th2 T-helper cells. It stimulates the growth of B cells and increases the number of Th2 T-helper cells at the site of inflammation.
(Choice C) IL-10 is an anti-inflammatory cytokine produced by macrophages and Th2 T-helper cells. IL-10 limits the production of pro-inflammatory cytokines (eg, interferon-gamma, IL-2, IL-3, TNF-α).
(Choice D) Leukotriene B4 is a metabolite of arachidonic acid. Its main function is to stimulate neutrophil migration to the site of inflammation.
(Choice E) Transforming growth factor-beta is released by macrophages and has anti-inflammatory roles in sepsis, including suppressing the release of IL-1 and TNF-α, and inhibiting lymphocyte proliferation.
Educational objective:
Tumor necrosis factor-alpha is released from activated macrophages and is one of the most important mediators of the systemic inflammatory response in sepsis. Other cytokines responsible for inducing the systemic inflammatory response include IL-1 and IL-6.