Effect of Histamine-Globulin Complex on Production of Anaphylactic

October 1968
Ind. J.:Physiol. & Pharmacol.
h this drug immediately
Letter to the Editor
are changed on alternate
or pus.
EFFECT OF mSTAMINE-GLOBULIN COMPLEX ON PRODUCTION OF
ANAPHYLACTIC SHOCK
Sir,
The anaphylactic reaction consists of antigen-antibody union which is followed by activation of proteolytic enzymes and liberation of toxic metabolites like histamine, 5-HT etc. (6).
Histamine is the major metabolite in anaphylactic shock in most species of animals (7, 8).
uthor for controlling skin
The preliminary clinical
t of work is still required
or of Pathology, Medical
d the sensitivity tests
encouragement, sugges-
In order to prevent anaphylactic shock, attempts to immunize animals against histamine
had been tried out in the past and sometimes reported to be successful (3, 4). However,
immunization against histamine is not an accepted practice, and as such, attempts were made to
re-evaluate this procedure. Injections of histamine may lead to eosinophilia, and eosinophils
have now been postulated to carry antihistamine substances (1). Another way of blocking
anaphylactic reaction would be the use of nonspecific globulins to act as blocking antibodies (5).
In order to combine the two approaches 0.15 mg of histamine base was mixed with 12.0 mg
of gamma-globulin to be contained in 1.0 ml of saline. This preparation has been termed as
histaglobin.
Histaglobin has been used subcutaneously for 12-21 days in treatment of various allergic
disorders like asthma (20 cases), migraine (1 case), and allergic urticaria (1 case) with beneficial
results in approximately 25 per cent of cases (9).
In view of the similarities of clinical bronchial asthma with experimental anaphylactic
shock (10), the preformed histaglobin complex was injected in experimental animals during
the incubation period.
The two important components of histamine action are (i) smooth muscle spasm, and
an increase in capillary permeability leading on to haemo-concentration because of seepage
of fluid from circulation. The former type of action is characteristically seen in bronchospasm
of the guinea-pig, and the latter in haemo-concentration produced in the mouse during anaphylaxis(11). Another way to study the increase in capillary permeability is to inject the antigen
locally in the paws of rats which had been sensitized 2 weeks before and were pretreated with
colloidal dye like Evan's blue (20 mgjkg body weight) immediately before such injections.
(ii)
Accordingly, guinea-pigs (200-400 g), albino rats (100-150 g) and albino mice (20-25 g)
of either sex were sensitized by subcutaneous injection of 50 per cent egg-white solution in
saline (7). B. pertussis vaccine was used along with the sensitizing dose in the latter two
speciesas recommended previously (2, 7). The challenging dose was injected intravenously
4-S weeks later in the guinea-pig and 12-14 days later in rats and mice. Guinea-pigs are normally
extremely sensitive to anaphylactic shock and as such minor degrees of protective effects
mightnot be detected when challenge is given intravenously; as such in some experiments
guineapigs were exposed to antigen aerosol (5 per cent egg-white solution in saline) for 2 min.
October 1968
Ind. J. Physiol. &.Pharmacoi.
214 Dutta et al.
in order to bring out minor differences in shock like state between the various groups. The
control animals were not given any further treatment, but the test groups of animals received
histaglobin during the incubation period. The dosage schedule of such pretreatments has
been shown in the Table I. In one set of experiments in the guinea-pig, attempts were made to
increase antibody output against histaglobin complex by simultaneous use of Freund's adjuvant.
TABLE
Animal species
1.
Guinea-pigs
Effect of histaglobin pretreatment
Pretreatment
No of
Daily dose
animals
6
nil
2.
18
3.
13
0.062-0.5
graded
nil
4.
13
5.
6.
7.
Mice
8.
9.
on anaphylactic shock in various species
(Histaglobin)
Method of
No. of days before
challenge
challenge
i.v.
nil
Mortality
5
i.v.
nil
aerosol
0.1 ml
10
aerosol
7
nil
nil
aerosol
4
7
0.6 rnl and Freund's
adjv.
nil
2 days only
17,16 days
nil
aerosol
3
i.v,
6
0.02 ml
8
i.v.
8
nil
nil
i.v.
7
7
8
ml
1. Broo
Lon
2. Dha
Asthl
10
10
Rats
I
Volume 12
Number 4
3. Far
4. Kar
41:1
18
5. Mo
siol.
6. San
136,
7. San
8. San
ana,
7
group)
9. Seh
His
The control and test animals were maintained under identical circumstances and challenged at the same time. The results have been shown in the Table I. It was seen that pretreatment with histaglobin complex had not modified the intensity of the anaphylactic reaction in any
one of the species employed.
10. Se
h
10.
i.v.
8
8
0.15 ml
(Experiments were in consecutive pairs, the first one of the pair being control group, second one test
11. Val
The local injection of antigen in rat paws in sensitized animals and in sensitized animals
pretreated with the histaglobin complex in a similar manner, failed to demonstrate any difference
between the two groups.
Thus, it would appear that immunization against histamine is not an effective method of
treatment of anaphylactic shock, and does not provide laboratory support for clinical use of
the histaglobin complex.
The authors are thankful to Shri A.V. Mody, Unichem Laboratories
for generous supply of histaglobin and for suggesting the problem.
Ltd.,
Bombay,
S.N. DUTIA,
B.D. MIGLANI,
R.K. SANYAL
Department of Pharmacology
Maulana Azad Medical College and Associated
Irwin and G.B. Pant Hospitals, New Delhi.
,.
October 1968
Ind. J. Physiol, &.Pharmacol.
n the various groups. The
t oups of animals received
f such pretreatments
has
'pig, attempts were made to
ususe of Freund's adjuvant.
Mortality
i.v.
S
i.v.
18
aerosol
y
REFERENCES
I. Broome, J. and R.K. Archer. Effect of equine eosinophils on histamine
Land. 193:446, 1962.
in vitro.
2. Dhar, H.L. and R.K. Sanyal. Mediators of anaphylactic shock in the mouse.
Asthma. 9 :85, 1963.
in various species
Method of
challenge
Letter to the Editor 215
Volume 12
Number 4
aerosol
1
aerosol
4
aerosol
3
i.v,
6
i.v.
8
i.v.
7
i~.
trol group, second one test
7
group)
I circumstancesand challengI. It was seen that pretreate anaphylacticreaction in any
3. Farmer, L. Experiments on histamine-refractoriness,J.
Nature,
Allergie
Immunol. 37:321,1939.
4. Karady, E.S. Histamine tolerance and anaphylactic death in sensitised guineapigs.
41:1, 1941.
5. Mongar, J.L. and H.O. Schild. A study of the mechanism of passive sensitization.
siol. 150:546, 1960.
6. Sanyal, R.K. Anaphylaxis in laboratory and clinical practice.
136, 1959.
Ibid.
J. Phy-
33:
J. Ind. Med. Assoc.
7. Sanyal, R.K. and G.B. West. Anaphylactic shock in the albino rat. J. Physiol.142:571,
1958.
8. Sanyal, R.K. and G.B. West. The relationship of histamine and 5·hydroxytryptamine
anaphylactic shock in different species. J. Physiol. 144:525,1958.
9. Scharadi, A., I. Gergely
and E. Kanter.
Histaglobin : Orv. Hetil. 107:1267, 1966.
U
to
Treatment of Tuberculotic-Asthma patients with
10. Schild, H.O., D.F. Hawkins, J.L. Mongar
and H. Herxheimer. Reactions of isolated
human asthmatic lung and bronchial tissue to a specific antigen. Lancet. 2:376, 1951.
11. Va7. N.M., E.T. lff and J.M. Peixoto, Int. Arch. Allergy. 30 : 268, 1~66.
als and in sensitized animals
to demonstrate any difference
is not an effective method of
ry support for clinical use of
aboratories Ltd.,
Bombay,
DUTIA,
MIGLANI,
.SANYAL
of Pharmacology
al College and Associated
t Hospitals, New Delhi.
'"