Farm Environment T Helper 1 Cytokine Asthma

Farm Environment Exposure in Early Childhood Induces T Helper 1-Cytokine Profiles and Asthma Protection

Farm Environment Exposure – Asthma

Update at BrainImmuneIn a recent study, published in Clinical & Experimental Allergy by Heidi Kääriö et al., using samples from the Protection Against Allergy-Study in Rural Environments (PASTURE) birth cohort, demonstrate that farm exposures (stables, hay barn, farm milk) at age 4.5 years is linked to amplified Th1-type cytokine production.

There have been recent advances into the understanding of how farming exposures might differentially affect various asthmatic phenotypes. Based upon age and type of farming exposures, a wide range of studies have demonstrated protective or deleterious effects of the farming environment on asthma conditions.

The evidence supporting the theory of farming exposures as variably protective against the development of asthma and in support of the “hygiene hypothesis” is strongest in several European pediatric cohorts.

The hygiene hypothesis, or the “Old Friends” hypothesis, suggests that one reason for the increasing incidence of chronic inflammatory disorders such as allergies, inflammatory bowel disease (IBD) and autoimmunity (e.g. Type 1 diabetes; multiple sclerosis) in developed countries since the mid-19th Century is the depletion from the urban environment of immunoregulation-inducing organisms that accompanied mammalian evolution.

In specific countries such as the United Kingdom and Australia, the prevalence of asthma and atopic skin reactivity has increased, while in other countries such as Hong Kong, Germany, and Italy there has been an increase in atopy, but not asthma. Further, numerous studies report an inverse correlation for atopy for children who were raised on a farm versus nonfarm children, suggesting that farming is protective of atopy.

The Allergy and Endotoxin Study (ALEX) conducted from 1999–2004 and the Prevention of Allergy Risk factors for Sensitization in children related to Farming and Anthroposophic Lifestyle (PARSIFAL) project conducted from 2001–2004 have been important studies demonstrating farming exposures as protective against atopic and asthmatic conditions.

The more recent GABRIELA studies demonstrate similar findings in relation to asthma and allergy as the ALEX and PARSIFAL studies. The GABRIELA study was a large European study, including 8,334 school children in Germany, Switzerland, and Austria, and demonstrated decreased prevalence of asthma and atopy in children exposed to farming environments compared to children not exposed to farming environments.

One of the GABRIELA studies looked at the settled dust from children’s rooms and evaluated it for culture of bacterial and fungal organisms. Gram negative bacterial rods in the study homes were noted to confer protection against atopy. This finding reinforces the theory of endotoxin burden protecting against the development of atopy in children.

Potential explanations for the immune-protective effects of these various farming exposures have focused on innate immune signaling pathways, particularly the highly conserved Toll-like receptor (TLR) recognition signaling pathways. In general, activation of TLRs enhance T-helper (Th)1 immune responses as opposed to the allergic, Th2 polarized immune responses. Including the theory that early farm exposure (including in utero) modulate the innate immune system.

In their study, published in Clinical & Experimental Allergy, Heidi Kääriö et al., the research group from Finland and Germany report that peripheral blood mononuclear cells (PBMCs) from farm children produced more Th1-associated cytokines such as IL-12 and interferon (IFN)-γ, and immunoregulatory cytokines such as IL-10. Interestingly, the number of farm exposures correlated with higher IFN-γ levels.

Children growing up on a farm have significantly less asthma, hay fever and atopic reactions. Farm exposure provides protection from childhood asthma and allergic diseases, but the causal mechanisms remain poorly understood.

It is also known that T helper (Th) 2-type cytokines such as interleukin (IL)-4, IL-5 and IL-13 drive allergic/asthma reactions, whereas Th1-type cytokines antagonize these effects.

Thus, growing up on a farm, in early childhood, and its related Th1-type immune responses may be linked to suppressed, allergy related Th2-type responses, and this may provide help explaining the protection of farming lifestyle on asthma and allergy development in children.

An Update

As per a recent 2021 opinion article by Erika von Mutius, a German pediatrician and allergologist, the protective effect of a traditional farm exposure on the development of childhood asthma and allergies as documented in numerous studies is very robust. According to this article there are two main pillars of the protective farm effect – the exposure to animal sheds, in particular cowsheds, and the consumption of unprocessed cow’s milk.

Keping in mind that cowsheds and unprocessed cow’s milk are “soups” containing myriads of potentially relevant elements. Moreover, the diversity of farm animal exposure during pregnancy has been associated with lower risk of atopic dermatitis and higher IFN-y and TNF-α levels in supernatants of cord blood mononuclear cells stimulated with LPS.

Finally, the diversity of the environmental and human nasal microbiome, respectively, have been associated with lower risk of asthma in the farm populations.

Source: Clin Exp Allergy, 2015 Sep 12. doi: 10.1111/cea.12636. [Epub ahead of print]