April 1999
Volume 54, pp. 398-399
A.W. Taylor-Robinson,
School of Biology,
University of Leeds,
Leeds, UK
Asthma, tuberculosis, cancer, myalgic encephalomyelitis,
and Gulf War
syndrome have all been linked recently to a shift in the
immune profile
favouring a T helper 2 (Th2) cell bias (1). In the UK,
this situation has
been associated with the multiple vaccinations given to
troops before Gulf
combat (2). This has led to the suggestion to manipulate
the immune
response in order to encourage the development of Th1
cells and thereby to
counter the effects of these conditions, but this has led
to concern that
this will not be achieved without some form of immunologic
penalty (1).
My concern, however, is the price we may be already paying
for the immune
deviation toward a Th2 profile.
The soldiers in question were immunized against anthrax,
cholera, plague,
tetanus, typhoid, and pertussis (whooping cough), all of
which require
potent Th2-inducing vaccines. This large antigen loading
further favours a
systemic shift toward a Th2 predominance and associated
cytokine profile
(1) and has raised
questions regarding the safety of the procedure. A UK
government report confirms that troops received a
pertussis vaccine as an
adjuvant for the anthrax vaccine, so that the latter was
effective from 7
weeks instead of 32 weeks. The use of pertussis vaccine in
this way was
highly experimental, relying on the preliminary findings of
Ministry of
Defence-sponsored research, and was performed despite a
warning by the
National Institute for Biological Standards and Control, a
UK regulatory
control body (2).
This highlights a possible serious drawback of combined
pertussis vaccine
use and is of considerable concern since pertussis
vaccination is known to
be an etiologic factor in the development of childhood
asthma (3). The
incidence of asthma is on the increase and so is the use of
multiple
vaccination procedures. When pertussis is combined with
diphtheria and
tetanus (the DTP vaccination given in the UK to 8-week-old
babies along
with Hib and, in some cases, tuberculosis), the same immune
deviation
develops, a bias towards Th2 responsiveness. The pertussis
vaccine may not
be the culprit in the case of asthma, but may be a marker
for the effects
of multiple vaccination, as it is not usually given in
isolation.
Apprehension about this apparent shift in immune cell
populations is clear.
In a Th2-dominant system, interleukins (IL) 4, 5, and 13
are upregulated,
along with excessive synthesis of IgE via clonal expansion
and secretion of
IL-4 (4). Combine this with the resultant enhanced
eosinophil activity, and
all the ingredients are present for atopic conditions such
as asthma,
eczema, hay fever, and food intolerances to develop. By
contrast, a bias
toward Th1-regulated cytokine synthesis would inhibit type
1
hypersensitivity reactions via IFN gamma, which
counterregulates IL-4 and
thereby decreases IgE production. The balance between IFN
gamma and IL-4
determines the level of IgE synthesis. This
interrelationship is key since
these cytokines are secreted by Th1 and Th2 cells,
respectively, supporting
the concept that immune balance is crucial if atopy is to
be avoided (4).
Multiple vaccinations shift this delicate balance,
favouring the
development of atopy and, perhaps, autoimmunity through
vaccine-induced
polyclonal activation leading to autoantibody production.
An increase in
the incidence of childhood atopic diseases may be expected
as a result of
concurrent vaccination strategies that induce a Th2-biased
immune response.What should be discussed is whether the prize of a reduction of
common infectious diseases through a policy of mass vaccination from birth is worth
the price of a higher prevalence of atopy.
1. Rook GAW, Zumla A.
Gulf War syndrome: is it due to a systemic shift in
cytokine balance towards a Th2 profile? Lancet
1997;349:1831-1833.
2. Butler D. Admission
on Gulf War vaccines spurs debate on medical records. Nature 1997;390:3-4.
3. Kemp T, Pearce N,
Fitzharris Pet al. Is infant immunization a risk factor for childhood asthma or
allergy? Epidemiology 1997;8:678-680.
4. Del Prete G. The
concept of type-1 and type-2 helper T cells and their
cytokines in humans. Int Rev Immunol 1998;16:427-455.
3. Mark A; Bjorksten B; Granstrom M. Immunoglobulin E
responses to diphtheria and
tetanus toxoids after booster with aluminium-adsorbed and
fluid DT-vaccines. Vaccine
1995 May;13(7):669-73
4. Gupta RK. Aluminum compounds as vaccine adjuvants.
Adv Drug Deliv Rev 1998
Jul 6;32(3):155-172
5. Vassilev TL.
Aluminium phosphate but not calcium phosphate stimulates the specific
IgE response in guinea pigs to tetanus toxoid. Allergy
1978 Jun;33(3):155-9 6. Rook
6. GA, Stanford JL. Give us this day our daily germs. Immunology Today
Mar;19(3):113-6
7. Taylor-Robinson
AW. Multiple vaccination effects on atopy. Allergy 1999
Apr;54(4):398-400
8. Hurwitz EL, Morgenstern H. Effects of diphtheria-tetanus-pertussis
or tetanus vaccination on allergies and allergy-related respiratory symptoms
among children and adolescents in the United States. J Manipulative Physiol
Ther 2000 Feb;23(2):81-90
9. Romagnani S. T-cell subsets (Th1 versus
Th2). Annals of Allergy, Asthma, &
Immunology 2000;85:9-21
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