HISTAMINE SENSITIVITY AND ANAPHYLACTIC RESPONSE
HISTAMINE SENSITIVITY AND ANAPHYLACTIC RESPONSE
III. THEORETICAL CONSIDÉRATIONS
LAURENCE FARMER
From the Allergy Clinic and the Achelis
Laboratory,
Lenox
Hill
Hospital,
New
York,
New York
Much évidence points to the fact that the symptoms of anaphylactic shock are
due to the libération of histamine from the tissues of sensitized animais in the
course of the antigen-antibody reaction1. There is, furthermore, considérable
though not complète parallelism between the anaphylactic response of a species
and its sensitivity to histamine2. Thus, species, which like the guinea pig, are
highly sensitive to histamine are eminently susceptible to anaphylactic shock;
species, which like the rat, are highly résistant to histamine cannot be made
anaphylactic under normal circumstances. The anaphylactic response of a
species therefore seems to be determined by its degree of histamine sensitivity.
We suggest that the degree of histamine sensitivity of a species, and subse-
quently its anaphylactic response, are determined by its adrenal cortex hormone
(or hormones).
Thèse contentions are based on the following observations in rats and
guinea pigs:
i
A.
Rats
(a) Adrenalectomy, which éliminâtes the source of cortin production, increases
this species' susceptibility to histamine poisoning3 and to anaphylactic shock4.
(b) Hypophysectomy, which leads to atrophy of the adrenal cortex6, exerts
the same effect on histamine sensitivity6 and anaphylactic response7.
(c) Administration of cortex hormone to adrenalectomized8 or hypophysec-
tomized6 rats restores their natural résistance to histamine to almost normal
levels.
B.
Guinea pigs
(a) Adrenalectomy enhances the susceptibility of guinea pigs to anaphylactic
shock9.
(b) Administration of adrenal cortex extract diminishes the anaphylactic
response of normal sensitized guinea pigs10.
il
(a) Administration of thyroid extract enhances the susceptibility of guinea
pigs to histamine poisoning11 and to anaphylactic shock12.
(b) Ascorbic acid déficient diet apparently exerts the same effects in this
species13.
We suggest that 1) the enhancement of histamine sensitivity and of anaphy-
lactic response, which follows the administration of thyroid extract or the feed-
365
366 LAURENCE FARMER
ing
of an
ascorbic acid déficient diet,
is due to
decrease
of the
cortin content
of
the adrenals;
2) the
decrease
of the
cortex hormone content
is due to
depletion
of
the
cholestérol stores
of the
adrenals (from which
the
cortex hormone
is
prob-
ably derived)
and
that
the
decrease
of the
cholestérol content
is
subséquent
to
the depletion
of the
ascorbic acid stores
in the
adrenals.
Thèse contentions are based
on the
f ollowing observations
:
(a) Thyroid extract
or
thyroxine administered
to
normal guinea pigs leads to
:
1.
diminution
of the
ascorbic acid content
of the
adrenals11,
M;
2.
depletion
of the
cholestérol stores
of the
adrenals16;
3.
hypertrophy (compensatory?)
of the
adrenal cortex16.
This hypertrophy
can be
prevented
by
administration
of
desoxycorticosterone,
and
to a
lesser degree
by
administration
of
ascorbic acid16.
(b) Ascorbic acid déficient diet
in
guinea pigs, which, like humans
and mon-
keys,
cannot synthesize vitamin
C,
leads
to:
1.
depletion
of the
ascorbic acid stores
of the
adrenals17;
2.
decrease
of the
cholestérol content
of
adrenals18;
3.
hypertrophy (compensatory?)
of the
adrenal cortex19;
4.
decrease
or
even complète depletion
of the
cortin content
of the
adrenals20;
5.
symptoms
of
adrenal insufnciency21.
SUMMARY
The histamine theory
of
anaphylaxis postulâtes that
the
symptoms
of
anaphy-
lactic shock
are the
symptoms
of
histamine poisoning.
In
expansion
of
this
theory,
we
suggest that
the
degree
of
histamine sensitivity
and
subsequently
of
anaphylactic response
is
determined
by the
adrenal cortex hormone
(or
hormones).
REFERENCES
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AND TUM
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HISTAMINE SENSITIVITY AND ANAPHYLACTIC RESPONSE
367
(11)
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(13)
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(15)
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:
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(16)
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:
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:
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:
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(19)
MAY, M. M.
:
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(20)
GIROUD,
A.,
AND SANTA,
N.: Absence
d'hormone corticale chez
les
ani-
maux carences
en
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1939.
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A.,
SANTA,
N.,
AND MAR-
TINET,
M.: Variations de l'hormone
corticale
en
fonction
de
l'acide
as-
corbique. Ibid., 134: 23, 1940.
GIROUD,
A.,
SANTA,
N.,MARTINET,M.,
M.,
AND
BELLON,
M. T.:
Dépend-
ance de l'hormone corticale vis-à-vis
de l'acide ascorbique. Ibid.,
134:
100,
1940.
(21)
GIROUD,
A.,
AND RATSIMAMANGA,
R.:
L'insuffisance surrénalienne de i'avi-
taminose
et
de l'hypovitaminose
C.
Presse méd., 48: 449, 1940.
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