WBR0490

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Immunology
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::A 4-year-old girl is brought to her pediatrician's office for right ear pain and chills for the past 2 days. Physical examination is remarkable for a fever of 38.7 °C (101.6 °F) and a bulging right tympanic membrane. She is diagnosed with acute otitis media and is prescribed a course of antibiotics. In addition, the patient is also prescribed acetaminophen to reduce her temperature. Which of the following inflammatory mediators is involved in the patient’s fever?]]
Answer A	AnswerA::Interleukin 1
Answer A Explanation	[[AnswerAExp::Interleukin 1 (IL-1) affects the activity of the hypothalamic thermoregulatory center, which leads to an increase in the core body temperature that results in fever. IL-1 is an endogenous pyrogen.]]
Answer B	AnswerB::Interleukin 2
Answer B Explanation	[[AnswerBExp::IL-2 is necessary for the growth, proliferation, and differentiation of T cells to become effector T cells. It is secreted by T helper cells.]]
Answer C	AnswerC::Interleukin 3
Answer C Explanation	[[AnswerCExp::IL-3 is secreted by basophils and activated T cells to support growth and differentiation of T cells from the bone marrow during an immune response.]]
Answer D	AnswerD::Interleukin 4
Answer D Explanation	[[AnswerDExp::IL-4 induces B-cell class switching to IgE and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cells.]]
Answer E	AnswerE::Interleukin 5
Answer E Explanation	[[AnswerEExp::IL-5 is a major regulator of eosinophil accumulation in tissues.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::The average oral temperature of the human body is 37 °C (98.6 °F) and is strictly regulated under physiologic conditions by the hypothalamus. Fever is considered the hallmark of immune system activation. It is defined as an elevation of core body temperature that occurs by a cytokine-mediated inflammatory response. Fever is mediated by 2 triggers: endogenous pyrogens/cytokines and exogenous pyrogens. Both endogenous and exogenous pyrogens can act together to induce fever. Exogenous compounds, such as lipopolysaccarides (LPS) on gram-negative bacteria, induce the production of endogenous pro-inflammatory cytokines, such as IL-1, IL-6, INF-alpha, and TNF. These cytokines cross the blood brain barrier and access the hypothalamic circulation, release local prostaglandins, and reset the hypothalamic thermal set-point to elevate the core body temperature. Clinically, fever is characterized by 3 phases: Chill/cold phase: Characterized by chills, cold sensations, and shivering. An increase in the core body temperature occurs to meet the new set-point via 2 mechanisms: cutaneous vasoconstriction to prevent peripheral heat loss and shivering muscle activity to generate heat. Fever phase: Characterized by warmth. In this phase, the generation and loss of heat are balanced and equal. Flush phase: Characterized by diaphoresis and cutaneous vasodilation. Set-point returns to normal, and body loses excessive heat. While some cytokines act as endogenous pyrogens, IL-10, arginine vasopressin, melanocyte-stimulating hormone, and glucocorticoids are considered endogenous antipyretics. Pharmacological agents may also be antipyretics, such as acetaminophen, aspirin, and NSAIDs. Fever should be differentiated from hyperthermia, whereby the temperature set-point in hyperthermia is not increased but the ratio of heat generation and heat dissipation is imbalanced. Heat stroke (exertional and non-exertional) and drug-induced hyperthermia are 2 examples of hyperthermia. Antipyretics are not effective in hyperthermia because the hyperthermia per se is not mediated by neither endogenous nor exogenous pyrogens. Accordingly, inhibition of these pyrogens does not yield any temperature reduction in hyperthermia. Instead, rapid cooling using ice water (for exertional heat stroke), passive cooling using fans (for non-exertional heat stroke), and dantrolene administration (for drug-induced hyperthermia) are more useful management options. Shown below is a table that summarizes the roles of interleukins and the main cells that secrete them. Educational Objective: Fever is considered the hallmark of immune system activation. It is defined as an elevation of core body temperature that occurs by a cytokine-mediated inflammatory response. Endogenous pro-inflammatory cytokines (endogenous pyrogens) include IL-1, IL-6, INF-alpha, and TNF. References: Dalal S, Zhukovsky DS. Pathophysiology and management of fever. J Support Oncol. 2006;4(1):9-16. First Aid 2014 page 205]]
Approved	Approved::Yes
Keyword	WBRKeyword::Interleukin, WBRKeyword::Fever, WBRKeyword::IL-1, WBRKeyword::Endogenous, WBRKeyword::Exogenous, WBRKeyword::Pyrogen, WBRKeyword::Hypothalamus, WBRKeyword::Core body temperature, WBRKeyword::Hypothalamic set-point
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Order in Linked Questions	LinkedOrder::