WBR0773

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Will Gibson)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Immunology
Sub Category	SubCategory::Gastrointestinal, SubCategory::General Principles
Prompt	[[Prompt::A 57-year-old Japanese man presents to the physician's office for abdominal fullness, weight loss, and excessive belching. Following appropriate work-up, he is diagnosed with advanced gastric cancer. The patient undergoes treatment with 5-fluorouracil and leucovorin rescue, but his tumor failed to show an objective response and therapy is discontinued. Several months later, he returns to the office appearing pale and asthenic. He suffers from dyspnea and weakness on minimal exertion. On physical examination, he has marked skeletal muscle atrophy and fat loss. Which of the following components most likely mediates the patient's condition?]]
Answer A	AnswerA::Interleukin-2 (IL-2)
Answer A Explanation	AnswerAExp::IL-2 is not a main mediator of cachexia syndrome. IL-2 is secreted by T cells and helps to activate other T cells.
Answer B	AnswerB::Tumor growth factor - beta (TGF-beta)
Answer B Explanation	AnswerBExp::TGF-beta is not a main mediator of cachexia syndrome. TGF-beta is a cytokine whose physiologic functions are varied and complex. Generally, TGF-beta is thought to reduce inflammation by inhibiting cell proliferation.
Answer C	AnswerC::IL-4
Answer C Explanation	AnswerCExp::IL-4 is not a main mediator of cachexia syndrome. IL-4 normally functions to induce the differentiation of naive T-helper cells in lymph nodes.
Answer D	AnswerD::Tumor necrosis factor - alpha (TNF-alpha)
Answer D Explanation	AnswerDExp::TNF-alpha is also known as cachectin because it is the main mediator of the syndrome of cachexia.
Answer E	AnswerE::Interferon-alpha (INF-alpha)
Answer E Explanation	[[AnswerEExp::INF-alpha is not a main mediator of cachexia syndrome. Nonetheless, IFN-gamma is frequently activated in cachexia. IFN-gamma is normally secreted by CD4+ Th1 cells and serves to activate nearby macrophages in the presence of a viral infection. The interferons as a family have direct antiviral activity and help to induce the expression of MHC-class II in virally infected cells.]]
Right Answer	RightAnswer::D
Explanation	[[Explanation:: The patient presents with signs and symptoms consistent with cachexia, a syndrome that is characterized by the presence of anorexia, fat and skeletal muscle wasting, severe asthenia, and fatigue. Cachexia affected patients have dyspnea and severe weakness on minimal exertion or even at rest. Cachexia usually is present in advanced chronic diseases, such as cancers, AIDS, tuberculosis, and other immunodeficiencies. In cancer patients, the presence of cancerous cells leads to chronic inflammation and activation of pro-inflammatory components, mainly tumor necrosis factor-alpha (TNF-alpha) which is also known as cachectin due to its major role in the syndrome, interferon-gamma (INF-gamma), and interleukin (IL)-1beta, and 6. The administration of antibodies against some of these components may sometimes help relieve the symptoms of cachexia. Educational Objective: TNF-alpha (cachectin) is the main mediator of cachexia. References: Gordon JN, Green SR, Goggin PM. Cancer cachexia. Q J Med. 2005; 98:779-788. Fearon, Kenneth CH, David J. Glass, and Denis C. Guttridge. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell metabolism 16.2 (2012): 153-166. First Aid 2014 page 231]]
Approved	Approved::No
Keyword	WBRKeyword::TNF-alpha, WBRKeyword::TNF, WBRKeyword::Alpha, WBRKeyword::Cachexia, WBRKeyword::Cachectin, WBRKeyword::Anorexia, WBRKeyword::Asthenia, WBRKeyword::Fatigue, WBRKeyword::Weakness, WBRKeyword::Dyspnea, WBRKeyword::Cancer, WBRKeyword::Gastric, WBRKeyword::Tumor, WBRKeyword::Tumor necrosis factor
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