The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that play a central role in the regulation of immune and inflammatory responses to infections or other insults.
IL-1 family is a group of 11 cytokines, which induces a complex network of proinflammatory cytokines and via expression of integrins on leukocytes and endothelial cells, regulates and initiates inflammatory responses.
IL-1 family members are synthesized as precursor proteins and cleaved into mature, active forms.
Members of this family include IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra), IL-18, IL-33, and IL-36α, β, γ, δ, ε. IL-1α and IL-1β are pro-inflammatory cytokines that are produced by immune cells in response to infection, injury, or stress.
They play key roles in initiating and regulating the inflammatory response.
IL-1Ra acts as a natural inhibitor of IL-1 signaling and helps to control excessive inflammation.
IL-18 is another pro-inflammatory cytokine that is involved in promoting the production of interferon-gamma and other inflammatory mediators.
IL-33 is an important cytokine that is involved in immune responses, allergic reactions, and inflammation.
IL-36 cytokines have pro-inflammatory functions and are involved in various inflammatory disorders.
IL-1α and IL-1β, the most studied members, have strong proinflammatory effects and share a natural antagonist, IL-1Ra.
Signaling in the IL-1 family allows binding to IL-1 receptor molecules, recruiting accessory proteins, and activating downstream signaling pathways with activation of various transcription factors, ultimately regulating and initiating inflammatory responses.
IL-1 is a cytokine production by various cells, playing a crucial role in the body’s inflammatory response to infection.
IL-1 promotes adhesion factors on endothelial cells, affects the hypothalamus, and causes fever, increased pain sensitivity, vasodilation, and hypotension.
IL-1 family members, including IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36ra, IL-37, and IL-38, have diverse functions and expression patterns.
IL-1 family members are involved in immune responses, inflammation, and regulation of energy metabolism.
IL-1ra is an important regulator of IL-1-induced expression, functioning as a competitive inhibitor of IL-1 receptor.
Recombinant IL-1ra (anakinra) is used to treat rheumatoid arthritis.
Cytokine-induced effector production involves the cytokine-dependent production of effector cytokines by differentiated T helper lymphocytes.
IL-1 has a major role in neuroinflammation and is associated with various diseases, including some cancers, ankylosing spondylitis, and Graves’ disease.
IL-1 receptor antagonist anakinra, approved for rheumatoid arthritis treatment, reduces symptoms and slows joint destruction.
It has also been prescribed for patients with indolent or smoldering myeloma at high risk of progression to multiple myeloma, providing a significant increase in progression-free disease years.
IL-1 family is a group of 11 cytokines, which induces a complex network of proinflammatory cytokines and via expression of integrins on leukocytes and endothelial cells, regulates and initiates inflammatory responses.
IL-1α and IL-1β possess strong proinflammatory effects.
They have a natural antagonist IL-1Ra (IL-1 receptor antagonist).
All of the members of IL-1 family, except IL-1Ra, are first synthesized as a precursor protein, which means it is synthesized as a long form of a protein which has to be proteolytically cleaved to a shorter, active molecule, which is generally called a mature protein.
The interleukin-1 superfamily has 11 members, which have similar gene structure.
IL-1α and IL-1β bind to the same receptor molecule, which is called type I IL-1 receptor (IL-1RI).
There is a third ligand of this receptor – the Interleukin 1 receptor antagonist (IL-1Ra), which does not activate downstream signaling, so it acts as an inhibitor of IL-1α and IL-1β signaling by competing with them for binding sites of the receptor.
IL-1 is produced by tissue macrophages, monocytes, fibroblasts, and dendritic cells, but is also expressed by B lymphocytes, NK cells, microglia, and epithelial cells, all forming an important part of the inflammatory response of the body against infection.
These cytokines increase the expression of adhesion factors on endothelial cells to enable transmigrate immunocompetent cells, such as phagocytes, lymphocytes and others, to sites of infection.
IL-1 affects the activity of the hypothalamus, the thermoregulatory center, which leads increase in body temperature (fever).
IL-1 is called an endogenous pyrogen.
Besides fever, IL-1 also causes hyperalgesia vasodilation and hypotension.
IL-1α plays a role in the nucleus by affecting transcription, as well as its extracellular receptor-mediated effects as a classical cytokine.
IL-33 also belongs in this group.
IL-1α is synthesized as a precursor protein and it is constitutively stored in the cytoplasm of cells of mesenchymal origin and in epithelial cells.
Monocytes and macrophages do not contain preformed IL-1α precursors, but rely on de novo synthesis.
Inflammatory responses in the absence of infection, as with ischemia are only dependent on IL-1α signaling via the Interleukin-1 receptor (IL-1R), rather than toll-like receptors (TLRs) signaling.
IL-1α also stimulates transcription and secretion of IL-1β from monocytes.
The initiator of immune responses is likely IL-1α precursor by induction of neutrophil infiltration.
IL-1β seems to be an amplifier of inflammation by recruitment of macrophages in the context of sterile inflammation.
IL-1β is synthesized as a precursor form protein only after stimulation, in contrast to IL-1α.
IL-1β expression is induced by transcription factor NF-κB after exposure of innate immune cells to alarmins.
IL-1ra is produced by monocytes, macrophages, neutrophils, fibroblasts, epithelial cells, Sertoli cells, microglia.
IL-1ra (Interleukin 1 receptor antagonist) is a naturally occurring protein in the body that blocks the effects of interleukin-1 (IL-1), which is a pro-inflammatory cytokine involved in immune responses and inflammation.
IL-1ra helps to regulate the immune system and maintain balance, preventing excessive inflammation.
It is also used as a therapeutic agent in the treatment of certain inflammatory diseases, such as rheumatoid arthritis and other autoimmune disorders.
Polymorphism of this gene is associated with an increased risk of osteoporotic fractures.
IL-1ra is used in the treatment of rheumatoid arthritis, as recombinant form of IL-1ra, anakinra.
IL-18 is known as a factor that induces the production of interferon gamma (IFN-γ).
IL-18 is a pro-inflammatory cytokine that shares similar biological effects to IL-12 and structural forms with the IL-1 family.
Together with IL-12 it mediates cellular immunity.
It binds to the IL-18Rα receptor.
IL-18 is produced by monocytes, macrophages, osteoblasts, keratinocytes, as an inactive precursor that is proteolytically cleaved to the active 18 kDa form.
IL-18 stimulates IFN-γ production by T cells and NK cells.
It acts either independently or synergizes with IL-12, promoting activation of the monocyte / macrophage system.
IL-18 and IL-12 inhibits IL-4 dependent production of IgE and IgG1 and, in turn, promotes IgG2 production by B cells.
IL-18 is involved in several serious inflammatory reactions.
The amount of IL-18 receptor mRNA in the endometrium as well as the ratio of the amount of binding protein to interleukin is demonstrably increased in patients with endomyosis compared to individuals without endomyosis.
IL-18 is also amplified in Hashimoto’s thyroiditis.
This interleukin has been shown to increase β amyloid production in neurons in Alzheimer’s disease.
IL-33 is synthesized as a 31-kDa precursor form and stimulates signaling that activates transcription factors as NF-κB and ERK, p38 and JNK MAPKs.
IL-33 is a dual function cytokine.
Besides its chromatin-associated function, it is constitutively expressed in healthy endothelial cells, because it acts as DAMPs after its release to extracellular space of cells in the context of immunologic not-silent cell death (necrosis or pyroptosis), and drives cytokine production in natural helper cells, nuocytes, Th2 lymphocytes, mast cells, basophils, eosinophils, invariant natural killer and natural killer T cells.
It is involved in allergic and parasite-induced inflammatory responses.
IL-36α is expressed in spleen, lymph nodes, tonsils, bone marrow, B-cells, and T lymphocytes.
IL-36β is expressed in the tonsils, bone marrow, heart, placenta, lung, testes, intestine, monocytes and B-lymphocytes.
IL-36γ is most produced by keratinocytes.
IL-36γ plays an important role in skin immunity and inflammation.
Expression is increased during chronic contact hypersensitivity, herpes simplex virus infection and psoriasis.
Expression is increased during chronic contact hypersensitivity, herpes simplex virus infection and psoriasis.
IL-36ra is highly expressed by keratinocytes, in psoriatic skin, placenta, uterus, brain, kidneys, monocytes, B-lymphocytes and dendritic cells.
IL-36ra acts as a non-specific inhibitor of inflammation and innate immunity. It inhibits IL-36α induced NF-κB activation.
Expression is increased during chronic contact hypersensitivity, herpes zoster.
IL-36ra is highly expressed by keratinocytes, in psoriatic skin, placenta, uterus, brain, kidneys, monocytes, B-lymphocytes and dendritic cells.
IL-36ra shares with IL-1ra 52% homology in the amino acid sequence.
IL-36ra acts as a non-specific inhibitor of inflammation and innate immunity.
IL-37 is expressed in most tissues, and non-specifically inhibits the inflammatory response and innate immunity.
IL-38 is expressed in the skin as well as in the tonsils, and regulates both innate and adaptive immunity: It binds to the soluble IL-1RI receptor.
IL-33 has a role in so called cytokine-induced effector cytokine production, meaning that a production of effector cytokines9 by differentiated T helper lymphocytes is cytokine dependent and can happen without antigen stimulation by T-cell receptor of these cells.
IL-33 in combination with some STAT5 activators, such as IL-2, IL-7 or TSLP, up-regulates expression of its own receptor on already differentiated Th2 lymphocytes.
IL-1 has a major role in neuroinflammation.
During neuroinflammation, there are increased levels of TNF and IL-1 in the brain, and their presence may cause the breakdown of the blood-brain barrier.
Polymorphisms in IL-1 genes have been found to contribute to genetic susceptibility to some cancers,, and to ankylosing spondylitis, and Graves’ disease.
The blockade of IL-1 activity (especially IL-1β) is a standard therapy for patients with autoimmune diseases or lymphomas.
Anakinra (IL-1Ra) is FDA-approved as a therapy for patients with rheumatoid arthritis: it reduces symptoms and slows joint destruction of this inflammatory disease.
In patients with indolent or smoldering myeloma with a high risk of progression to multiple myeloma, in combination with other medication, IL-1Ra provides a significant increase in the number of years of progression-free disease in its recipients.
IL-1 family is a group of 11 cytokines, which induces a complex network of proinflammatory cytokines and via expression of integrins on leukocytes and endothelial cells, regulates and initiates inflammatory responses.
IL-1α and IL-1β are the most possess strong proinflammatory effects.
They have a natural antagonist IL-1Ra (IL-1 receptor antagonist).
Nine IL-1 superfamily members occur in a single cluster on human chromosome two.
IL-18 and IL-33 are on different chromosomes.
IL-33 and IL-18 have been included into the IL-1 superfamily due to structural similarities, overlap in function and the receptors involved in their signalling.
The similar feature of and is that their precursor forms can bind to their respective receptors and can activate signal transduction.
The interleukin-1 superfamily has 11 members.
IL-1 is intensely produced by tissue and activated immune cells, such as macrophages, and monocytes in response to infection, injury, or other inflammatory stimuli.
IL-1 has a major role in neuroinflammation.
During inflammation, there are increased levels of and IL-1 in the brain, and their presence may cause the breakdown of the blood-brain barrier.
in IL-1 genes have been found to contribute to genetic susceptibility to some cancers.
The blockade of IL-1 activity is a standard therapy for patients with autoimmune diseases or lymphomas.
Anakinra 9IL-1Ra) is FDA-approved as a therapy for patients with rheumatoid arthritis-reduces symptoms and slows destruction of this inflammatory disease.
It has also been prescribed to patients with smoldering/indolent myeloma with high risk of progression to myeloma.
In combination with other medication, IL-1Ra provides a significant increase in the number of years of progression-free disease in its recipients.