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 subsequently 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 hypophysectomized6 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 anaphylactic response, which follows the administration of thyroid extract or the feed365
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 probably 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 following 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 monkeys, 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 anaphylactic 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
(1) F ARMER, L.: Histamine in anaphylaxis
and allergy. Bull. New York Acad.
Med., 16: 618, 1940.
(2) SCHMIDT, G. W., AND STAEHELIN, A.:
Histaminempfindlichkeit und anaphylaktischeReaktionen. Ztschr.f.
Immunitàtsforsch., 60: 222, 1929.
WYMAN, L. C. AND TUM SUDEN, C :
Blood pressure and reactions to
histamine in the rat after hypophysectomy and adrenalectomy. Am.
J. Physiol., 109: 115, 1934.
(7) MOLOMUT, N.: The effect of hypophysectomy on immunity and hyper-
(3) MARMORSTON - GOTTESMAN, J., AND
GOTTESMAN, J.: Use of histamine as
standard test for diminished re-
sensitivity in rats. J. Immunol.,
37: 113, 1939.
(8) MARMORSTON - GOTTESMAN, J., AND
(6) PERLA, D., AND ROSEN, S. H.: Effect
of hypophysectomy on natural re-
87: 327, 1922.
(10) WOLFRAM, J., AND ZWEMER, L.: Cor-
sistanceinsuprarenalectomizedrats.
J. Exper. Med., 47: 503, 1928.
(4) FLASHMAN, D. IL: The effect of suprarenalectomy on active anaphylactic
shock in the white rat, J. Inf. Dis.,
38:461,1926.
WYMAN, L. C.: Anaphylaxis in suprarenalectomized rats. Am. J.
Physiol., 89: 356, 1929.
(5) SMITH, P. E.: Hypophysectomy and
replacement therapy in rats. Am.
J. Anat., 45: 205, 1930.
sistance of adult albino rats to
histamine poisoning. Arch. Path.,
20: 222, 1935.
PERLA, D.: Effect of injections of
cortin on résistance of suprarenalectomized rats to large amounts of
histamine. Proc. Soc. Exper. Biol.
& and Med., 28: 1022, 1931.
ROSE, B.:The effect of cortin and
desoxycorticosterone acétate on the
ability of the adrenalectomized rat
to inactivate histamine. Am. J.
Physiol., 127: 780, 1939.
(9) KÉPINOW, L : Surrénales et anaphylaxie. Compt. rend. Soc. de biol.,
tin protection against anaphylactic
shock in guinea pigs. J. Exper.
Med., 61:9,1935.
HISTAMINE SENSITIVITY AND ANAPHYLACTIC RESPONSE
(11) FARMER, L.,
AND FRIBOURG,
R.:
Studies on histamine sensitivity
and anaphylactic response. The effect of thyroid extract. Proc. Soc.
Exper. Biol. & Med., 50: 208, 1942.
(12) SAVINI,E., ANDSAVINI,TH.: Thyroïde
et anaphylaxie. Compt. rend. Soc.
de biol., 78: 198, 1915.
KÉPINOW, L.: Glande thyroïde et
anaphylaxie. Ibid., 88: 846, 1923.
(13) GIROUD, A., GIROUD, P., RATSIMAMANGA, R., AND RABINOWICZ, M.:
367
of adrenals and livers of différent
animais. Biochem. J., 27: 960, 1933.
DECARO,L. : Ueber die Faehigkeit von
Gewebe Ascorbinsaeure zu fixieren
(im Normalzustand und in Avitaminose C). Ztschr. f. Physiol.
Chem., 223: 229, 1934; Ueber die
Menge Vitamin C, die zur Konstanthaltung des normalen Reduktionswertes tierischer Gewebe noetig
ist. Ibid., 240:179,1936.
GIROUD, A., AND LEBLOND, C. P.:
Pouvoir antianaphylactique de l'aVariations de la teneur des tissus en
cide ascorbique chez le cobaye; imacide ascorbique (vitamine C).
portance de l'alimentation et du
Compt. rend. Soc. de biol., 118:
taux de l'acide ascorbique sur la
1179, 1935.
sensibilité de l'organisme, Compt. (18) MOURIQUAND, G., AND LEULIER : Avitarend. Soc. de biol., 123: 1146, 1936.
minose C (avec ou sans tuberculose).
SARTORI, C. : Influenza dell' avitamiCholesterine du sang et des surrénales. Compt. rend. Acad. d. se,
nosi sull' anafilassi. Pathologica,
17: 160, 1925.
181: 434, 1925.
SERENI, E.: Richerche sulla anafilassi
RANDOIN, L., AND MICHAUX, A. : Vari(V) ; anafilassi ed avitaminosi. Boll.
ations comparative de la teneur des
d. Soc. ital. di biol. sper., 2:254,1927.
surrénales en eau, acides gras et
FARMER, L. AND KASSMAN, S. R.:
cholestérol chez le cobaye normal
Studies on histamine sensitivity and
et chez le cobaye soumis à un régime
anaphylactic response. The effect
déséquilibré par absence de vitamine
antiascorbutique, Ibid., 183: 1055,
of vitamin C déficient diet. Am.
J. Clin. Path., 13: 7, 1943.
1926.
(14) DEMOLE, V., AND IPPEN, F.: Die anti-
NAGAYAMA, T., AND TAGAYA, T.: The
lipoid metabolism of the guinea pig
thyreotoxische Wirkung von Asfed on a vitamin C free diet. J.
corbinsaeure. Ztschr. f. physiol.
Biochem., 11: 225, 1929/30.
Chem., 235: 226, 1935.
MOSONYI, J.: Einfluss des Schild- (19) MAY, M. M. : Das Verhalten von Schilddruesenhormons auf den Vitamin C
druese und Nebennieren beim experi—Stoffwechsel.
Ibid., 237: 173,
mentellen Skorbut und unter dem
1935.
Einflusse von Vitamin C (Redoxon).
PLAUT, F., AND BÙLOW, M.: Die
Ztschr. f. Vitaminforsch., 6: 239,
Abnahme des C-Vitamins im Liquor
1937.
cerebrospinalis als Merkmal ges- (20) GIROUD, A., AND SANTA, N.: Absence
teigerter Stoffwechselvorgaenge bei
d'hormone corticale chez les aniMalaria und bei Thyreoidinzufuhr.
maux carences en acide ascorbique.
Klin. Wchnschrf., 14: 1318, 1935.
Compt. rend. Soc. de biol., 131:1176,
1939.
NESPOR, E.: Influence de la thyroïde
sur les reserves de vitamine C.
GIROUD, A., SANTA, N., AND MARCompt. rend. Soc. de biol., 122: 427,
TINET, M.: Variations de l'hormone
1936.
corticale en fonction de l'acide ascorbique. Ibid., 134: 23, 1940.
(15) HOEN,E.,LANGEFELD, H., ANDOEHME,
GIROUD, A., SANTA, N.,MARTINET,M.,
C. : Ueber die Beziehungen zwischen
M., AND BELLON, M. T.: DépendSchilddruese und Nebennieren. Enance de l'hormone corticale vis-à-vis
dokrinologie, 21: 305, 1939.
de l'acide ascorbique. Ibid., 134:
(16) HERRING, P. T. : The effect of thyroid100, 1940.
feeding on the weight of the suprarenals and on their adrenalin con- (21) GIROUD, A., AND RATSIMAMANGA, R.:
tent. Quart. J. Exper. Physiol.,
L'insuffisance surrénalienne de i'avi11: 47, 1917.
taminose et de l'hypovitaminose C.
Presse méd., 48: 449, 1940.
(17) SVIRBELY, J. S.: Ascorbic acid content