Biomedical Engineering Reference
In-Depth Information
Table 9.4
The range of cells capable of producing IL-1
T-lymphocy tes
B-lymphocytes
Monocytes/macrophages
NK cells
Large granular lymphocytes
Keratinocytes
Chondrocytes
Vascular endothelial cells
Fibroblasts
Astrocytes
Dendritic cells
Microglia
Glioma cells
and some studies suggest that IL-1s can induce a biological response only upon binding to the
type I receptor.
The exact IL-1-mediated mechanism(s) of signal transduction remain to be clarifi ed. A number
of different signal transduction pathways have been implicated, including involvement of G-pro-
teins. IL-1 has also been implicated in activation of protein kinase C by inducing the hydrolysis of
phosphatidylethanolamine.
9.3.1 The biological activities of interleukin-1
IL-1 mediates a wide variety of biological activities:
•
It is a pro-infl ammatory cytokine, promoting the synthesis of various substances such as
eicosanoids, as well as proteases and other enzymes involved in generating infl ammatory
mediators. This appears to be its major biological function.
•
It plays a role in activating B-lymphocytes, along with additional cytokines, and may also play
a role in activating T-lymphocytes.
•
Along with IL-6, it induces synthesis of acute-phase proteins in hepatocytes.
•
It acts as a co-stimulator of haematopoietic cell growth/differentiation.
The relative prominence of these various biological activities depends largely upon the quanti-
ties of IL-1 produced in any given situation. At low concentrations, its effects are largely paracrine,
e.g. induction of local infl ammation. At elevated concentrations, it acts more in an endocrine man-
ner, inducing systematic effects, such as the hepatic synthesis of acute-phase proteins, but also
induction of fever (hence the name, endogenous pyrogen) and cachexia (general body wasting,
such as that associated with some cancers). Many of these biological activities are also promoted
by TNF, which is another example of cytokine redundancy.
In addition to IL-1α and -1β, a third IL-1-like protein has been identifi ed, termed IL-1 receptor
antagonist (IL-1R
). As its name suggests, this molecule appears to be capable of binding to the
IL-1 receptors without triggering an intracellular response.
α
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