Hygiene hypothesis

From Wikipedia, the free encyclopedia

In medicine, the hygiene hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms (e.g. gut flora), and parasites increases susceptibility to allergic diseases by modulating immune system development.[1]

Contents

[edit] History

First proposed by David P. Strachan in an article published in the British Medical Journal (now BMJ), in 1989,[2] the hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were presumably exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that has been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents (see Current theories below).

[edit] Mechanism of action

Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Many bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis stated that insufficient stimulation of the TH1 arm of the immune system lead to an overactive TH2 arm, which in turn led to allergic disease.[3]

The first proposed mechanistic explanation for the hygiene hypothesis cannot explain the rise in incidence (similar to the rise of allergic diseases) of several TH1-mediated autoimmune diseases, including inflammatory bowel disease (IBD), multiple sclerosis (MS), and type I diabetes. The major proposed alternative mechanistic explanation is that the developing immune system must receive stimuli (from infectious agents, symbiotic bacteria, or parasites) in order to adequately develop regulatory T cells, or it will be more susceptible to autoimmune diseases and allergic diseases, because of insufficiently repressed TH1 and TH2 responses, respectively.[4] To use a rough analogy, an unbridled immune system (without regulatory T cells) has the dynamic of a rowdy, unchaperoned beer party. It is likely to overreact to slight or non-existent insults (analogous to allergic disease) and may even attack members of its own party (analogous to autoimmune disease). The role of the T regulatory cells of the immune system is similar to that of the bouncer, keeping the beer party in check.

[edit] Current theories

The hygiene hypothesis has expanded to include exposure to several varieties of microorganisms and parasites, with which humans coexisted throughout much of our evolutionary history, as necessary for balanced and regulated immune system development.[5] In recent times, the development of hygienic practices and effective medical care have diminished or eliminated exposure to these microorganisms and parasites during development. Examples of organisms that may be important for proper development of T regulatory cells include lactobacilli, various mycobacteria, and certain helminths.[6]

Epidemiological data supports the hygiene hypothesis. The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.[7] The use of antibacterial cleaning products has also been associated with higher incidence of asthma, along with birth by Caesarean section rather than vaginal birth.[8][9] However, the studies investigating these links showed only tenuous correlation between the factors described and the conditions they are theorized to cause.

[edit] See also

[edit] References

  1. ^ Strachan DP. Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax 55 Suppl 1:S2-10.: S2-10, 2000.
  2. ^ Strachan DP. Hay fever, hygiene, and household size. BMJ 299: 1259-1260, 1989.
  3. ^ Folkerts G, Walzl G, Openshaw PJ. Do common childhood infections 'teach' the immune system not to be allergic? Immunol Today 2000; 21(3):118-120. PubMed
  4. ^ Guarner F, Bourdet-Sicard R, Brandtzaeg P, Gill HS, McGuirk P, van EW, Versalovic J, Weinstock JV and Rook GA. Mechanisms of disease: the hygiene hypothesis revisited. Nat Clin Pract Gastroenterol Hepatol 3: 275-284, 2006. PubMed
  5. ^ Gold DR,Wright R (2005). "Population disparities in asthma". Annu Rev Public Health 26: 89-113. doi:10.1146/annurev.publhealth.26.021304.144528. PMID 15760282. 
  6. ^ Rook GA,Brunet LR (2005). "Old friends for breakfast". Clin Exp Allergy 35 (7): 841-2. doi:CEA2112 [pii 10.1111/j.1365-2222.2005.02112.x]. PMID 16008666. 
  7. ^ Marra F, Lynd L, Coombes M "et al." (2006). "Does antibiotic exposure during infancy lead to development of asthma?: a systematic review and metaanalysis". Chest 129 (3): 610-8. doi:129/3/610 [pii 10.1378/chest.129.3.610]. PMID 16537858. 
  8. ^ Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell, CR (2007). "A meta-analysis of the association between Caesarean section and childhood asthma". Clin. and Exper. Allergy online ahead of print: 629. doi:10.1111/j.1365-2222.2007.02780.x. 
  9. ^ Zock JP, Plana E, Jarvis D "et al." (2007). "The use of household cleaning sprays and adult asthma: an international longitudinal study". Am J Respir Crit Care Med 176 (8): 735-41. doi:200612-1793OC [pii 10.1164/rccm.200612-1793OC]. PMID 17585104. 

[edit] Additional references

1. Camateros P, Moisan J, Henault J, De SJ, Skamene E and Radzioch D. Toll-like receptors, cytokines and the immunotherapeutics of asthma. Curr Pharm Des 12: 2365-2374, 2006.

[edit] External links