Biomedical Engineering Reference
In-Depth Information
4.
CYTOKINES
In our model, we postulated "information molecules"
H
and
K
that were
elevated when harm was done to the host or when pathogens were being killed.
The levels of
H
and
K
were assumed to directly modify cellular behavior. In
fact, matters are more complicated. Information molecules typically bind to cel-
lular receptors, which in turn induce the secretion by the cell of signalling mole-
cules that can be lumped under the term "cytokines." To give one example, there
is evidence that mycobacterial 65-kD heat shock protein induces T cells to se-
crete tumor necrosis factor (TNF) and, later, interleukin-6 (IL-6) and IL-8 (10).
4.1. The Observed Actions of Cytokines
Matters might be simple if there were a one-to-one correspondence between
the appearance of a cytokine and the triggering of some task or function. But
that is not the case. Indeed, consider the following points cI-cIV that character-
ize the pleiotropic action of cytokines (1,8).
(cI) Upon ligation of receptors, several cytokines are normally produced.
Here are three examples: (i) ligation of the LPS (lipopolysaccharide) receptor
induces IL-1, 6, 8, 12 and TNF
; (ii) ligation of the Fc
receptor by IgG induces
IL-10; and (iii) ligation of scavenger receptors by apoptotic bodies induces
TGF
, PGE-2 and PAF.
(cII) A cytokine often effects several actions of a given cell (for example,
IL-4 influences switches to IgM, IgG, and IgE).
(cIII) Sets of cytokines can induce a variety of different actions of different
cells, for example, ligation of the LPS receptor induces B cells to increase anti-
body production and switch toward the IgG isotype, liver cells to secrete acute
phase proteins, hypothalamus cells to elevate body temperature, neutrophils to
become mobilized, and vascular cells to be more permeable.
(cIV) A given function is typically affected by several cytokines (the IgG
switch is affected by IL-2,4,6 and interferon-
).
The standard view of cytokines, and it is a correct one, is that
cytokines
command
. (The switch from IgM to Ig is "commanded" in B cells, at least in
vitro, by the list of cytokines in cII above.) In the language of control theory, in
this view cytokines are the front end of the actuator machinery that is activated
by sensor-receptors.
4.2. Cytokines as Bearers of Information
I propose an alternative view: that
cytokines transmit information
. I believe
that regarding them as bearers of information is another correct way to charac-
