Cytokines in Immune Response Quiz
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Questions and Answers

What effect does IL-1β have on IL-25 and IL-33 production during helminthic infection?

  • It suppresses both IL-25 and IL-33 production. (correct)
  • It enhances both IL-25 and IL-33 production.
  • It enhances IL-25 production but suppresses IL-33 production.
  • It has no effect on either IL-25 or IL-33 production.

Besides type 2 polarization, in which condition has IL-33 been shown to play a role?

  • Type 1 diabetes
  • Osteoporosis
  • Multiple Sclerosis
  • Fungal infection (correct)

In cardiovascular disease models, what protective role does IL-33 play?

  • It exacerbates cardiac hypertrophy.
  • It has no effect on plaque formation or cardiac hypertrophy
  • It reduces atherosclerotic plaque formation and cardiac hypertrophy (correct)
  • It increases atherosclerotic plaque formation.

What is the role of IL-33 in visceral adipose tissue regarding immune cells?

<p>It induces ILC2-dependent increases in eosinophils and M2 macrophage polarization. (C)</p> Signup and view all the answers

Increased serum concentrations of ST2 have shown predictive value for which of the following conditions?

<p>Graft versus Host Disease after stem cell transplantation (C)</p> Signup and view all the answers

What is one way that IL-33 is similar to IL-1β?

<p>They are both activated by the same protein (B)</p> Signup and view all the answers

Which of the following is NOT a mechanism to activate IL-18?

<p>Decoy Receptors (A)</p> Signup and view all the answers

How does IL-18 relate to IFN-γ, regarding its discovery?

<p>It was initially identified as a factor that induces IFN-γ (D)</p> Signup and view all the answers

Which cell type is NOT explicitly mentioned as containing the IL-18 precursor?

<p>Macrophages (D)</p> Signup and view all the answers

What is the relationship between the tertiary structure of IL-18 precursor and the IL-37 precursor?

<p>They have a close structural relationship. (A)</p> Signup and view all the answers

What is one function of IL-18 which is related to a specific cell response?

<p>An important component of polarized Th1 cell and NK cell responses (C)</p> Signup and view all the answers

Which condition below is NOT mentioned as being associated with IL-18?

<p>Rheumatoid arthritis (C)</p> Signup and view all the answers

In models of age-related macular degeneration, what role does IL-18 play?

<p>It is protective. (B)</p> Signup and view all the answers

What is a specific biological process that IL-18 requires caspase-1 for?

<p>Induction of IFN-γ (D)</p> Signup and view all the answers

What can be implied about the role of caspase-1 in IL-18 dependent Fas sustained liver injury?

<p>IL-18 does not require it for this process (B)</p> Signup and view all the answers

What is one specific approach to studying phenotypes in caspase-1-deficient mice?

<p>Assess if any observed effect is due to reduced IL-1β or IL-18 activity. (C)</p> Signup and view all the answers

What is the primary function of IL-36Ra?

<p>To act as an antagonist for IL-1Rrp2, preventing IL-36 activity. (A)</p> Signup and view all the answers

How does IL-36Ra impact the IL-36-elicited pathway?

<p>It negatively regulates the pathway, thus reducing the production of IL-23, IL-17, and IL-22. (A)</p> Signup and view all the answers

Mutations in the IL-36Ra gene are associated with which condition?

<p>A rare, life-threatening form of psoriasis. (D)</p> Signup and view all the answers

What is a key characteristic of the TIR8 receptor?

<p>It has a single Ig domain and a TIR domain with atypical substitutions. (D)</p> Signup and view all the answers

Where is TIR8 predominantly expressed in the body?

<p>In several tissues, such as the kidney, digestive tract, liver, lung, and lymphoid organs. (C)</p> Signup and view all the answers

What are the primary effects of TIR8 on inflammatory pathways?

<p>It inhibits NF-kB and JNK activation by interfering with adaptor molecule recruitment. (C)</p> Signup and view all the answers

In which context does TIR8 regulate mTOR kinase activity?

<p>In Th17 lymphocytes and intestinal epithelial cells. (B)</p> Signup and view all the answers

What is the main role of TIR8 in the context of inflammatory responses to infections as indicated by studies with deficient mice?

<p>To play a non-redundant role in dampening potentially detrimental inflammatory responses associated with various infections. (B)</p> Signup and view all the answers

What is the primary function of the nuclear localization sequence (NLS) found in the pro-piece of IL-1α?

<p>To enable nuclear transport of the entire IL-1α precursor by allowing it to bind to the DNA. (C)</p> Signup and view all the answers

How do the downstream events following receptor engagement of IL-1α and IL-1β generally compare?

<p>They are largely similar, with the main differences being their cellular sources and release mechanisms. (A)</p> Signup and view all the answers

In what context have neutralizing antibodies to IL-1α shown promising results in a clinical trial?

<p>In patients with cachexia (wasting syndrome) associated with terminal colon cancer. (D)</p> Signup and view all the answers

Besides differences in cell source and release mechanisms, what is another key difference found between IL-1α and IL-1β?

<p>IL-1α is known to localize to the nucleus, while IL-1β is not. (D)</p> Signup and view all the answers

According to the information given, what role does IL-1α play in the context of cancer development?

<p>It is a component of the intrinsic pathway linking genetic events causing cancer and cancer-related inflammation. (A)</p> Signup and view all the answers

What is the implication of discovering IL-1's involvement in different forms of cancer-related inflammation across various organs?

<p>Anti-IL-1 strategies require a detailed understanding of its precise role in each specific neoplasm for effective exploitation. (A)</p> Signup and view all the answers

Which statement best describes the intrinsic pathway of cancer development, as it relates to IL-1α?

<p>It links genetic events like Ras mutations with cancer-related inflammation, involving IL-1α. (D)</p> Signup and view all the answers

Based on the information provided, what is the role of IL-1 in the extrinsic pathway related to cancer?

<p>It is related to cancer development in different organs such as the pancreas, skin, and liver, which is driven through underlying inflammatory conditions. (A)</p> Signup and view all the answers

What is one of the primary benefits of using anakinra in treating certain conditions?

<p>Rapid and sustained reduction in inflammation. (B)</p> Signup and view all the answers

In the context of autoinflammatory diseases, what process leads to the release of IL-1β?

<p>Dysregulation of caspase-1 in activated monocytes. (C)</p> Signup and view all the answers

Which of the following diseases is NOT mentioned as a condition that canakinumab can treat?

<p>Pustular psoriasis (C)</p> Signup and view all the answers

What is the specific target of canakinumab?

<p>IL-1β (C)</p> Signup and view all the answers

What has been observed in limited trials using a neutralizing monoclonal anti-IL-1α antibody?

<p>Reduced disease severity across various conditions. (B)</p> Signup and view all the answers

What is the role of IL-1 family members in the context of lymphoid cells?

<p>They are key players in the differentiation and function of innate and adaptive lymphoid cells. (D)</p> Signup and view all the answers

In which area is canakinumab being tested in a large trial?

<p>Cardiovascular pathology (D)</p> Signup and view all the answers

Which of the following has NOT been treated by a neutralizing monoclonal anti-IL-1α antibody in limited trials?

<p>Recurrent gout attacks (A)</p> Signup and view all the answers

Which study demonstrated the interplay between IL-1 homologue IL-1F7b and IL-18-binding protein?

<p>Bufler et al., 2002 (A)</p> Signup and view all the answers

Which study explored the role of single Ig IL-1 receptor-related molecule/Toll IL-1R8 in regulating Th2 immune response?

<p>Bulek et al., 2009 (D)</p> Signup and view all the answers

According to the provided studies, which of the following is true about IL-33?

<p>It is inactivated by caspase-1 after maturation (D)</p> Signup and view all the answers

Which of the following is NOT explicitly identified as a process linked to IL-1β in the studies provided?

<p>regulation of Th2 immune response (D)</p> Signup and view all the answers

Which cellular process directly involves a pathway identified by Chen et al. (2007)?

<p>sterile inflammatory response triggered by dying cells (B)</p> Signup and view all the answers

Which of these studies examined the role of IL-33 in the context of chronic obstructive lung disease?

<p>Byers et al., 2013 (B)</p> Signup and view all the answers

The study by Carmi et al. (2013) primarily investigated which aspect of IL-1β?

<p>its role in the early tumor cell-induced angiogenic response (A)</p> Signup and view all the answers

Which study specifically utilizes animal models to investigate inflammasome-mediated disease?

<p>The study mentioned with no author listed with the text 'Inflammasome-mediated disease animal models...' (D)</p> Signup and view all the answers

Flashcards

IL-33

A protein involved in both type 2 immune responses and other pathological conditions, affecting innate and adaptive immune cells.

ST2

A protein that acts as a decoy receptor for IL-33, potentially regulating its activity.

ILC2

A type of immune cell involved in type 2 responses, often associated with helminth infections and allergy.

Immune Polarization

A process in which immune cells are programmed to respond in a specific way, often associated with specific pathogens.

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Cleavage

The process of a substance becoming active, often through a change in its structure.

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Inactive Precursor

A protein that is not functional until cleaved by another enzyme.

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Cytokine-Inducing Factor

A substance that triggers the production of a specific cytokine, like interferon-gamma.

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Decoy Receptor

A type of receptor that does not activate a signaling pathway, acting as a 'dummy' receptor to regulate the activity of other receptors.

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IL-1α's role in cancer

IL-1α plays a role in both the intrinsic and extrinsic pathways of cancer development.

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IL-1α and the intrinsic pathway

IL-1α contributes to the initiation of cancer by promoting inflammation and influencing genetic alterations like Ras mutations.

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IL-1α and the extrinsic pathway

IL-1α exacerbates existing inflammatory conditions, which in turn increase cancer risk in specific organs.

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IL-1α vs IL-1β

IL-1α and IL-1β have distinct cellular origins and release mechanisms, but their downstream effects are largely similar.

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IL-1α's nuclear localization

IL-1α, unlike IL-1β, can localize to the nucleus and participate in transcription, indicating a deeper role within the cell.

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IL-1α's nuclear localization sequence (NLS)

A specific sequence of basic amino acids within IL-1α's propiece allows it to bind to DNA and influence gene expression.

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IL-1α and cancer therapy

Antibodies targeting IL-1α are being investigated in clinical trials for their potential to treat cancer.

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IL-1α therapy's challenges

Due to the complex and organ-specific nature of inflammation in cancer, targeting IL-1α in treatment requires careful consideration.

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What is IL-18?

A protein found in the body that is involved in regulating immune responses, especially those related to Th1 cells and NK cells. It is produced by certain types of cells, including macrophages.

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How is IL-18 activated?

IL-18 needs to be processed (changed) by caspase-1 to be fully active and trigger a response.

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What are the roles of IL-18 in the immune system?

IL-18 plays a role in a variety of immune responses, including inflammation, defense against infections, and autoimmune diseases. It can contribute to both beneficial and harmful effects on the body.

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How is IL-18 similar to IL-1α?

IL-18 is similar to IL-1α in terms of its location in the body and its role in initiating immune responses.

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What is the role of IL-18 in macrophage-NK cell interactions?

IL-18 is involved in the interplay between macrophages and natural killer (NK) cells, which are both important players in the immune system.

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What diseases are associated with IL-18?

IL-18 has been linked to a variety of diseases, including autoimmune disorders, cardiovascular diseases, and metabolic diseases.

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What to consider when studying caspase-1 deficient mice?

When studying the effects of caspase-1 deficiency on immune responses, it is important to consider whether the changes are related to reduced IL-1β, IL-18, or both.

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Can IL-18 be protective in some conditions?

IL-18 has been shown to be protective in some diseases, highlighting its complex and multifaceted role in the body.

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What is IL-36Ra?

IL-36Ra is a protein that blocks the activity of IL-36, a molecule involved in inflammation. It acts as a specific antagonist for IL-1Rrp2 receptor.

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How does IL-36Ra regulate inflammation?

IL-36Ra plays a role in regulating the immune response by preventing the production of pro-inflammatory cytokines like IL-23, IL-17, and IL-22. These cytokines contribute to inflammatory skin conditions like psoriasis.

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What happens when IL-36Ra is dysfunctional?

Mutations in the gene encoding IL-36Ra can lead to a severe form of psoriasis, a skin condition characterized by inflammation and scaling. This suggests that IL-36Ra is essential in preventing excessive inflammatory responses.

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What is TIR8?

TIR8 is a protein that inhibits the activation of NF-kB and JNK, both key molecules involved in inflammation.

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How does TIR8 work?

TIR8 inhibits the activation of NF-kB and JNK by interfering with the assembly of signaling complexes triggered by TLRs and IL-1R family members. It acts as a negative regulator of inflammatory responses.

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Where is TIR8 found in the body?

TIR8 is expressed in various tissues, including the kidney, digestive tract, liver, lung, and lymphoid organs, suggesting a wide-ranging role in regulating inflammation.

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What are the consequences of TIR8 deficiency?

Studies in mice lacking TIR8 have shown increased susceptibility to infections such as tuberculosis, candidiasis, aspergillosis, and P.aeruginosa infection, indicating a critical role of TIR8 in protecting against these infections.

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What is another role of TIR8?

TIR8 can also regulate mTOR kinase activity, which is important for the development and function of T helper 17 cells (Th17 cells) that play a role in immune responses.

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What is Anakinra?

Anakinra is a drug that blocks the action of interleukin-1 (IL-1), a protein that plays a role in inflammation. It is used to treat conditions like rheumatoid arthritis, gout, and systemic juvenile idiopathic arthritis.

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How does Anakinra work?

Anakinra works by rapidly and persistently reducing inflammation, often leading to a decrease in steroid use, especially in children with systemic juvenile idiopathic arthritis.

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What is Canakinumab?

Canakinumab is a monoclonal antibody that specifically targets IL-1β. It is used to treat certain inflammatory conditions such as CAPS (Cryopyrin-Associated Periodic Syndromes), systemic onset juvenile idiopathic arthritis, and gout.

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What are monoclonal antibodies?

Monoclonal antibodies are specific, targeted proteins that bind to and neutralize specific molecules, such as IL-1β or IL-1α. They play a crucial role in treating various inflammatory conditions by blocking the actions of these molecules.

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What is the IL-1 Family?

The IL-1 family is a group of proteins that play a critical role in inflammation. They are involved in regulating the immune system, influencing the differentiation and function of immune cells, and contributing to the development of inflammatory conditions.

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What is the significance of IL-1's role in immune cell differentiation and function?

The discovery of the role of IL-1 in regulating immune cell differentiation and function has highlighted its importance in both innate (natural) and adaptive (learned) immune responses. This finding has revolutionized our understanding of inflammation and opened up new avenues for treating inflammatory diseases.

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What does the IL-1F7b and IL-18-binding protein complex do?

A complex of IL-1F7b (an IL-1 homologue) and IL-18-binding protein reduces the activity of IL-18.

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What role do long-lived epithelial progenitor cells play in COPD?

Long-lived epithelial progenitor cells that continuously produce the cytokine IL-33 contribute to chronic obstructive lung disease (COPD).

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What is the role of IL-1beta in early tumor angiogenesis?

IL-1beta, a pro-inflammatory cytokine, plays a critical role in the early angiogenic response triggered by tumor cells, promoting blood vessel growth in tumors.

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How is IL-33 inactivated?

IL-33, a cytokine with IL-1-like activity, is inactivated through maturation by the enzyme caspase-1.

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What is the key pathway for sterile inflammatory response?

Dying cells trigger a sterile inflammatory response, a type of inflammation that doesn't involve pathogens, through a specific pathway involving caspase-1 and ASC

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What is the role of single Ig IL-1 receptor-related molecule/Toll IL-1R8 in the immune system?

This molecule, single Ig IL-1 receptor-related molecule/Toll IL-1R8, plays a crucial role in regulating the Th2 immune response, which is involved in allergic reactions and parasitic infections.

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What do animal models reveal about the importance of innate and adaptive immunity in inflammatory diseases?

Animal models of inflammatory diseases reveal that innate immunity, but not adaptive immunity, plays a significant role in these diseases.

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Study Notes

Interleukin-1 Family: Back to the Future

  • Interleukin-1 (IL-1) is a key mediator of innate immunity and inflammation.
  • The IL-1 family includes 7 agonist ligands, 3 receptor antagonists, and an anti-inflammatory cytokine (IL-37).
  • The family includes 6 receptor chains that form 4 signalling receptor complexes.
  • Decoy receptors (IL-1R2, IL-18BP) and negative regulators (TIR8 or SIGIRR, IL-1RAcPb) help maintain a balance between immune response and inflammation.
  • All innate immune cells express, or are affected by IL-1 family members.
  • IL-1 family members are involved in the differentiation and function of polarized innate and adaptive lymphoid cells.

Introduction

  • IL-1 was the first interleukin identified as a very potent cytokine, affecting various organs and cells.
  • IL-1's pleiotropic effects are widely observed, ranging from resistance against microbes to roles in the hypothalamus and T lymphocytes.
  • The TIR domain, found in IL-1 receptors and Toll-like receptors (TLRs), plays a critical role in sensing microbes and tissue damage.
  • Discovery of decoy receptors, particularly IL-1R2, challenged the conventional definition of receptors.
  • Decoy receptors evolved as mechanisms to regulate cytokine actions.

Overview of IL-1 and IL-1R Family Members

  • The IL-1 family contains 7 agonist ligands (IL-1α, IL-1β, IL-18, IL-33, IL-36α, β, and γ), 3 receptor antagonists (IL-1Ra, IL-36Ra and IL-38) and an anti-inflammatory cytokine (IL-37).
  • The IL-1R family includes 11 molecules involved in signaling via MyD88, a key adaptor.
  • Receptor complexes (IL-1R1/IL-1RAcP, IL-33R/IL-1RAcP, IL-18R, IL-36R).
  • IL-1α and IL-1β are crucial in inflammation, though distinct roles exist.
  • IL-1α is involved in sterile inflammation, while IL-1β requires caspase-1 activation.
  • Caspase-1 activation is part of the inflammasome, triggered by various stimuli (e.g. microbial infection, tissue damage).

IL-1

  • Acts on virtually all cells and organs in various diseases (autoinflammatory, autoimmune, infectious, degenerative).
  • Key roles in immunity, such as fever (activation of the hypothalamic-pituitary-adrenal (HPA) axis) and leukocyte recruitment, including the acute phase response.
    • Fever: IL-1 is an endogenous pyrogen.
    • Leukocyte recruitment: Up-regulation of adhesion molecules.
  • Plays a role in autoinflammatory diseases, as well as in cancer, including tumor angiogenesis and metastasis.

IL-33

  • Involved in type 2 immunity and inflammation.
  • Acts on a wide range of immune cells, including innate lymphoid cells type 2 (ILC2s), T helper 2 (Th2) cells, and alternatively activated macrophages.
  • Role in asthma, fibrosis, and responses to parasites.
  • GWAS indicates links to asthma risk.
  • Protective role in various conditions (e.g., parasites, fungi, viral infections).
  • Potent driver of type 2 inflammatory conditions and their associated symptoms.

IL-18

  • Is closely related to IL-1β in terms of production, processing, and receptor usage.
  • Plays a crucial role in Th1 cell responses, NK cell responses, and the interaction between macrophages and NK cells.
  • Implicated in autoimmune diseases, myocardial pathology, and metabolic syndrome.
  • Plays a role in the inflammatory cascade, impacting the severity of certain conditions (e.g., heart ischemia).

IL-36

  • IL-36 family (IL-36α, β, and γ) work through the IL-1Rrp2 receptor complex using IL-1RAcP as a coreceptor.
  • Receptor antagonist IL-36Ra, sharing structural similarities with IL-1Ra, plays an important regulatory role in dampening inflammation.

IL-37

  • An anti-inflammatory cytokine.
  • Functions in transcription suppression via interactions with Smad3.
  • Involved in mitigating the effects of IL-1 and TLRs.
  • Suppresses IL-25 and IL-33, thereby mitigating inflammation.

Negative Regulators

  • The IL-1 system has several negative regulators: receptor antagonists, decoy receptors, and TIR8.
  • IL-1R2 acts as a decoy receptor.
  • IL-18BP (IL-18 binding protein) prevents IL-18 from binding its receptor.
  • TIR8 or SIGIRR suppresses inflammation by interacting with multiple signalling pathways.

Orchestration of Innate and Adaptive Immuncompetent Cells

  • IL-1 family members regulate various arms of the immune response.
  • Modulation of T cell polarization: IL-18 and IL-33 influence Th1 and Th2 cell differentiation.
    • Th17 cells, regulated by IL-1 beta.
    • NK cell activation and responses.
  • Interactions between innate and adaptive cells.

Therapeutic Strategies

  • IL-1 receptor antagonists (e.g., anakinra) are effective in a wide range of disorders.
  • Neutralizing antibodies (e.g., canakinumab) are currently being explored.

Concluding Remarks

  • IL-1 family members are critically important in tissue homeostasis and inflammation.
  • Negative regulation of the IL-1 system is essential to prevent excessive inflammation.
  • Deeper understanding of the IL-1 system can lead to better treatment strategies for various diseases.

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The Interleukin-1 Family: Back to the Future PDF

Description

Test your knowledge on the role of various cytokines such as IL-1β, IL-25, IL-33, and IL-18 in immune responses and disease conditions. This quiz covers their effects during helminthic infections, cardiovascular diseases, and more. Dive into the intricate functions of these important immune mediators!

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