Untitled - D Ank Unlimited

cytokine assays 209 cytokine-specific subunit
belong to a family of receptors that share a gp130 signal
tranducer subunit in common, which explains some of
the similar functions these molecules have on various
tissues. In IL2 signal transduction with respect to T cell
growth, IL4, IL7, and IL15 also promote growth of T cells.
IL4, IL7, and IL15 use the IL2 receptor γ chain, which
accounts for the redundant functions of these cytokines as
T cell growth factors. Cytokines have been named on the
basis of the cell of origin or of the bioassay used to define
them. This system has led to misnomers such as “tumor
necrosis factor,” which is more appropriately termed
an immunomodulator and pro-inflammatory cytokine.
The interleukins now number 17, even through IL8 is, in
fact, a member of the chemokine cytokine family. The
chemokines share a minimum of 25% amino acid homology,
are similar in structure, and bind to seven rhodospin
superfamily transmembrane spanning receptors. The CC
or γ chemokines are encoded by genes on chromosome
17. CXC chemokines attract neutrophils, whereas CC
chemokines attract monocytes.
cytokine assays
Tests based on the biological properties, immunological
recognition (ELISA or radioimmunoassay), competitive
binding to receptor molecule, and inference from transcription
of the mRNA. Each method has advantages and disadvantages.
Bioassays are quite sensitive and verify biological
activity of the cytokine but are not always reproducible or
specific. By contrast, immunoassays are reproducible and
specific but not nearly as sensitive as bioassays.
cytokine autoantibodies
Autoantibodies that may inhibit cytokine functions and lead
to cytokine deficiency. Autoimmune disease may occur, and
the action of the cytokine may be inhibited. By contrast,
these autoantibodies may serve as cytokine-specific carriers
in the circulation. For example, insulin autoantibodies may
prolong the release of active insulin to the tissues, leading
to hypoglycemia in nondiabetics and a significant decrease
in the exogenous insulin requirement in diabetic patients.
AIDS patients may develop autoantibodies against IL2,
and antibodies against TNFα have been used successfully
to treat rheumatoid arthritis. Both normal and inflammatory
disease patients may develop autoantibodies against
IL1α. Cytokine activity is enhanced even in the presence
of cytokine autoantibodies in vivo by a mechanism that
delays rapid catabolism of cytokines from the circulation.
The clinical relevance of cytokine autoantibodies in vivo
remains to be determined. However, these autoantibodies
portend a poor prognosis in any disease. Methods for
cytokine autoantibody detection include bioassays, immunometric
assays, and blotting techniques.
cytokine inhibitors
Prostaglandins, especially prostaglandin E2 (PGE2),
synthesized by monocytes and macrophages, have been
suggested to provide feedback inhibition of cytokine synthesis
in vivo. Cytokine production inhibition is a possible
mechanism whereby PGE exerts its anti-inflammatory
effect. Treating rats with a monoclonal antibody specific
for murine IL6, which mediates the acute phase response,
led to increased survival in Escherichia coli shock.
β-adrenergic agonists increase cAMP levels and THP-1
cells and suppress synthesis of TNFα. A β-adrenergic
antagonist can abolish inhibition of TNFα synthesis.
Isoproterenol, a β-adrenergic agonist, inhibits TNFα
synthesis. Dexamethasone and cAMP phosphodiesterase
(PDE-IV) inhibitors suppress TNFα secretion by lipopolysaccharide
(LPS)-activated human monocytes. IL1 receptor
antagonist (ILlra) is the only known natural cytokine
antagonist. It inhibits the binding of IL1α and IL1β to their
cell surface receptors. Selected antibiotics such as fluoroquinolones,
clarithromycin, and tetrandrine inhibit IL1 and
TNFα synthesis. Some anti-inflammatory drugs also have
cytokine inhibitor capacity.
cytokine receptor classes
Include the immunoglobulin receptor superfamily, the
hematopoietic/cytokine receptor superfamily, the nerve
growth factor receptor superfamily, the G protein coupled
receptor superfamily and the other family, and the receptor
tyrosine or serine kinases plus an unclassified group.
cytokine receptor families
A classification system of cytokine receptors according
to conserved sequences or folding motifs. Type I receptors
share a tryptophan–serine–X–tryptophan–serine (or
WSXWS) sequence on the proximal extracellular domains.
Type I receptors recognize cytokines with a structure of
four α-helical strands, including IL2 and granulocyte
colony-stimulating factor (G-CSF). Type II receptors are
defined by the sequence patterns of type I and type II
interferon receptors. Type III serve as receptors for tumor
necrosis factor (TNF) (p55 and p75). CD40, nerve growth
factor receptor, and Fas protein have sequences homologous
to those of type III receptors. A fourth family of receptors
has extracellular domains of the immunoglobulin (Ig)
superfamily. IL1 receptors as well as some growth factors
and colony-stimulating factors have Ig domains. The
fifth family of receptors displays a seven-transmembrane
α-helical structure. This motif is shared by many of the
receptors linked to GTP-binding proteins.
cytokine receptors
Sites on cell surfaces where cytokines bind, thus leading to
new cell activities that include growth, differentiation, and
death. Cytokines bind to these high affinity cell surface
receptors that share some features in common. They have a
high affinity for ligand. Typically a hundred to a few thousand
receptors are present per cell. Most cytokine receptors
are glycosylated, integral, type I membrane proteins.
Functional cytokine receptors are usually complex structures
requiring the formation of homologous or heterologous
associations between receptor chains. A cytokine receptor
group may share chains dubbed “public subunits” and ordinarily
engage in signal transduction. Unique chains termed
“private subunits” usually determine binding specificity. By
contrast, receptors of the chemokine family belong to the
serpentine superfamily and span the membrane seven times;
they do not appear to form multimeric complexes.
cytokine receptors, soluble
Soluble cytokine receptors include IL1, type I-R, IL1, Type
II-R, IL2Rα, IL2Rβ, IL4R, IL5Rα, IL6Rα, gp130 IL6Rβ
ciliary neurotrophic factor (CNF)-Rα, and growth hormone
R. Most of these function by blocking ligand binding.
cytokine-specific subunit
A multimeric cytokine receptor polypeptide chain that
interacts stereospecifically with the target cytokine. It is
responsible for the specificity of a receptor for a particular
cytokine.
C