Biology Reference
In-Depth Information
International Congress on Lymphokines (Géry and Waksman, 1972).
There are two known members in this family of proteins, IL-1α and IL-
1β, and both bind to the same receptors and produce similar biological
responses. In several studies, IL-1β has been detected consistently in the
plasma of sepsis patients, while IL-1α has rarely been seen. IL-1β is first
produced as a soluble 31 kDa (269 amino acids) inactive protein, which
is converted to the active 18 kDa form by IL-1β−converting-enzyme
(ICE, also known as caspase-1). The crystal structure of IL-1β has been
obtained and shows that this cytokine consists of a β-barrel with four
triangular faces forming a tetrahedron (Priestle
et al.
, 1988, 1989).
Similarly to TNFα, IL-1β is produced mostly by monocytes and
macrophages, but it can be released by most cell types. IL-1 genes are
not expressed in the absence of stimulation. Several agents are able to
induce the transcription of these genes including LPS, complement
components, and cytokines (TNFα, INF-γ, GM-CSF, and IL-1 itself)
(Colotta
et al.
, 1998). As part of homeostasis, Interleukin-1 receptor
antagonist (IL-1ra), a naturally occurring cytokine produced by many
cell types, binds to the IL-1 receptor without triggering any cellular
responses. IL-1ra circulates in the plasma soon after infection along with
soluble IL-1 receptors and together both act as anti-inflammatory
mediators. There are two known IL-1 receptors: type 1 (or IL-1RI,
expressed mostly by fibroblasts and T cells) and type 2 (or IL-1RII,
expressed predominantly in monocytes, PMN, and B cells). Although
both receptors recognize both IL-1 forms, IL-1RI has a higher affinity
for IL-1α (K
d
= 10
-10
M versus 10
-9
M), whereas IL-1RII binds IL-1β
more effectively (K
d
= 10
-9
to 10
-10
M versus 10
-8
M) (McMahan
et al.
,
1991). Administration of IL-1 to rodents and primates induced the
symptoms of sepsis in the animals (Okusawa
et al.
, 1988, Fischer
et al.
,
1991). Alternatively, blockade of IL-1 receptors with antibodies
protected rats and primates from suffering the full symptoms of sepsis
such as hypotension and tachycardia (rapid heart rate) during exposure of
these animals to
E. coli
, suggesting a critical role for IL-1 in sepsis. IL-1
has been known to activate macrophages and lymphocytes and stimulate
secretion of other cytokines such as IL-2, IL-3, IL-6, and interferon
(IFN) (Dinarello, 1989). Furthermore, IL-1 had been reported to promote
the activation of other cells including helper-T cells, NK cells, and tumor
