With great interest we read the article by Benn et al. (1) about the
association between childhood infection and risk of atopic dermatitis.
From this cohort study of siblings it was concluded that clinically
apparent infectious diseases do not protect from the development of atopic
diseases. However, we think that this conclusion needs reconsideration.
The current understanding of the immunopathogenesis of atopic diseases
relies on the predominance of Th2-type immune response suggesting over-
production of Th2-type cytokines (2). Due to the existing cross-regulatory
interplay between Th1-type and Th2-type immune response (3),
susceptibility for allergic reactions may increase when Th2-type cytokines
are over-produced or when Th1-type cytokines such as interferon-gamma are
suppressed. Accordingly, the "hygiene hypothesis" suggests that a lack of
triggers for Th1-type immune response like exposure to infections,
endotoxins and dirt in childhood would result in a persistence of Th2-type
immune response responsible for allergic disease (4).
Considering the interplay between infectious diseases and cytokine changes
it is important to classify pathogens. It is well known that cytokine
patterns differ considerably between types of infections: acute infections
with intracellularly growing pathogens, predominantly viruses but also
mycobacteria and parasites evoke Th1-type immune response involving
cytokines like interferon-gamma, whereas acute infections with common
bacteria preferentially induce humoral (= Th2-type) immune response
associated with antibody production but not involving Th1-type cytokines,
e.g. significant elevation of neopterin concentrations, which indicate
production of interferon-gamma, is only found in patients suffering from
pneumonias of viral origin but not from bacterial origin (5).
Common bacterial infection probably may increase the risk for atopic
disease whereas virus infections are less likely. However, even in the
latter case it cannot be excluded that counter-regulatory activity
necessary to slow-down the activated Th1-type immune response during acute
infection may provoke overwhelming formation of Th2-type cytokines.
In conclusion, it will strongly depend on the classification of infections
during early childhood whether a firm conclusion can be drawn that
infections are or are not involved in promoting the development of
allergic diseases.
Katharina Schroecksnadel, Christian Murr, Dietmar Fuchs
Institute of Medical Chemistry and Biochemistry, Innsbruck Medical
University, and Ludwig Boltzmann Institute of AIDS Research Innsbruck,
Austria
1. Benn CS, Melbye M, Wohlfahrt J, Bjorksten B, Aaby P. Cohort study
of sibling effect, infectious diseases, and risk of atopic dermatitis
during first 18 months of life. BMJ 2004;328:1223-7.
2. Romagnani S. Immunologic influences on allergy and the TH1/TH2
balance. J Allergy Clin Immunol 2004;113:395-400.
3. Strachan DP. Hay fever, hygiene and houshold size. BMJ 1989;299:1269-
60.
4. Shearer GM, Clerici M.T helper cell immune dysfunction in
asymptomatic, HIV-1-seropositive individuals: the role of TH1-TH2 cross-
regulation.
Chem Immunol 1992;54:21-43.
5. Denz H, Fuchs D, Hausen A, et al. Value of urinary neopterin in
the differential diagnosis of bacterial and viral infections. Klin
Wochenschr 1990;68:218-22.
Rapid Response:
Childhood infection and risk of atopic dermatitis
With great interest we read the article by Benn et al. (1) about the
association between childhood infection and risk of atopic dermatitis.
From this cohort study of siblings it was concluded that clinically
apparent infectious diseases do not protect from the development of atopic
diseases. However, we think that this conclusion needs reconsideration.
The current understanding of the immunopathogenesis of atopic diseases
relies on the predominance of Th2-type immune response suggesting over-
production of Th2-type cytokines (2). Due to the existing cross-regulatory
interplay between Th1-type and Th2-type immune response (3),
susceptibility for allergic reactions may increase when Th2-type cytokines
are over-produced or when Th1-type cytokines such as interferon-gamma are
suppressed. Accordingly, the "hygiene hypothesis" suggests that a lack of
triggers for Th1-type immune response like exposure to infections,
endotoxins and dirt in childhood would result in a persistence of Th2-type
immune response responsible for allergic disease (4).
Considering the interplay between infectious diseases and cytokine changes
it is important to classify pathogens. It is well known that cytokine
patterns differ considerably between types of infections: acute infections
with intracellularly growing pathogens, predominantly viruses but also
mycobacteria and parasites evoke Th1-type immune response involving
cytokines like interferon-gamma, whereas acute infections with common
bacteria preferentially induce humoral (= Th2-type) immune response
associated with antibody production but not involving Th1-type cytokines,
e.g. significant elevation of neopterin concentrations, which indicate
production of interferon-gamma, is only found in patients suffering from
pneumonias of viral origin but not from bacterial origin (5).
Common bacterial infection probably may increase the risk for atopic
disease whereas virus infections are less likely. However, even in the
latter case it cannot be excluded that counter-regulatory activity
necessary to slow-down the activated Th1-type immune response during acute
infection may provoke overwhelming formation of Th2-type cytokines.
In conclusion, it will strongly depend on the classification of infections
during early childhood whether a firm conclusion can be drawn that
infections are or are not involved in promoting the development of
allergic diseases.
Katharina Schroecksnadel, Christian Murr, Dietmar Fuchs
Institute of Medical Chemistry and Biochemistry, Innsbruck Medical
University, and Ludwig Boltzmann Institute of AIDS Research Innsbruck,
Austria
dietmar.fuchs@uibk.ac.at
1. Benn CS, Melbye M, Wohlfahrt J, Bjorksten B, Aaby P. Cohort study
of sibling effect, infectious diseases, and risk of atopic dermatitis
during first 18 months of life. BMJ 2004;328:1223-7.
2. Romagnani S. Immunologic influences on allergy and the TH1/TH2
balance. J Allergy Clin Immunol 2004;113:395-400.
3. Strachan DP. Hay fever, hygiene and houshold size. BMJ 1989;299:1269-
60.
4. Shearer GM, Clerici M.T helper cell immune dysfunction in
asymptomatic, HIV-1-seropositive individuals: the role of TH1-TH2 cross-
regulation.
Chem Immunol 1992;54:21-43.
5. Denz H, Fuchs D, Hausen A, et al. Value of urinary neopterin in
the differential diagnosis of bacterial and viral infections. Klin
Wochenschr 1990;68:218-22.
Competing interests:
None declared
Competing interests: No competing interests