Review Question - QID 217256

This patient presents with altered mental status, suprapubic and costovertebral angle tenderness, fever, hypotension, tachycardia, and tachypnea in the setting of elevated acute-phase reactants including C-reactive protein and ferritin, which are indicative of acute pyelonephritis secondary to an ascending urinary tract infection. IL-6 is primarily responsible for the generation of acute-phase reactants.

Cytokines are key regulators of the cellular immune response. They function to induce vascular changes at the site of inflammation, recruit immune cells, cause differentiation of target cells, and signal to distant organs. Frequently tested cytokines include IL-1, IL-4, IL-6, IL-10, IL-12, and IL-23. IL-1 is secreted by macrophages and causes fever, acute inflammation, and endothelial expression of cell adhesion molecules. IL-4 is secreted by Th2 cells, induces differentiation of T-cells into Th2 cells, and promotes class-switching of immunoglobulins to IgG and IgE. IL-6 is secreted by macrophages and is responsible for fever and acute-phase reactant generation by the liver. Acute-phase reactants are proteins that are up-regulated during acute inflammatory states, such as ferritin, C-reactive protein, and fibrinogen. IL-10 is secreted by regulatory T-cells and decreases the immune response by inhibiting macrophages and dendritic cells. IL-12 is secreted by macrophages, induces differentiation of T-cells into Th1 cells, and activates natural killer cells. IL-23 induces the differentiation of T-cells into Th17 cells, which play a key role in clearance of certain pathogens and in autoimmunity.

Gulhar et al. review the physiology of the acute-phase reactants. They discuss the role of IL-6 as the primary cause of acute-phase reactant production in the liver.

Incorrect Answers:
Answer 1: IL-1 is responsible for stimulating fever and activating expression of adhesion molecules in endothelial cells. It is upregulated in any acute inflammatory reaction. However, it does not induce acute-phase reactant production by the liver.

Answer 2: IL-4 plays a key role in the formation of Th2 cells, which regulate the humoral immune response against extracellular parasites, bacteria, and toxins. It also plays a key role in inducing immunoglobulin class-switching to some IgG types and IgE. It has no role in the stimulation of acute-phase reactant production.

Answer 4: IL-10 is secreted by regulatory T-cells to dampen the immune response once the acute infection is controlled. This helps limit damage to the body’s own cells. Because of its inhibitory effect on macrophages, it would decrease acute-phase reactant production.

Answer 5: IL-12 plays a key role in the formation of Th1 cells and activation of natural killer cells, which provide defense against intracellular viral and bacterial pathogens. It has no role in the stimulation of acute-phase reactant production.

Bullet Summary:
IL-6 is the primary cytokine responsible for acute-phase reactant generation in the liver.