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.
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