Report on Immune Stimulation

Editor’s note: At the BEMS 2008 meeting Jan Cuppen reported on a series of experiments performed with an ELF stimulus that showed an apparent enhancement of the immune system in carp cells, and whole animimal goldfish, chicken broilers, shrimp, and piglets. This work, using relatively simple fields appeared to be of great interest to many members at that meeting and could have significant impacts on the efficiency of food stock production in the future. Given that, we asked him for a synopsis of the work, printed below.

REPORT ON IMMUNE STIMULATION IN FARMED ANIMALS BY LF EMF

Jan Cuppen, Ph.D., Immunent BV, The Netherlands

Introduction

Parts of this work were done in collaboration with Geert Wiegertjes at Wageningen University, Anton Beynen and Mohammed Elmusharaf at Utrecht University, and Willem Smink from FIS BV in The Netherlands.

At the BEMS 2008 meeting we reported on a series of experiments performed with an ELF stimulus that showed an apparent enhancement of the immune system in carp cells, and whole animal, goldfish, chicken broilers, shrimp, and piglets. This work, using relatively simple fields (detailed in the Cuppen reference given at the end of this article), was of such interest to many members that we describe it briefly here, with references, so that members may learn more about our work. We believe that a key characteristic of our work is that we work with large numbers of animals, so the experiments are sensitive for effects, but with limited sophistication (and cost) of measurements. This work could, potentially, have significant impacts on the efficiency of food stock production in the future.

Some of our data has been published (Cuppen et al. 2007) and further papers are in preparations.

Hypothesis

Several publications have demonstrated the production of cytokines, increased immune parameters and stress effects and concluded that EMF causes stress at the cellular level and that this leads to production of cytokines and consequently biological response, including immune response. This has led Simkó and Mattson (2004) to proposes that macrophage activation could be effected through ROS due to short term EMF exposure.

In Immunology, Matzinger (2002) recently proposed that immune response is not only due to the presence of non-self cells but also needs the presence of promotors called “danger signals” like HSP’s, Interleukins and other cytokines. Danger signals are formed when cells get stressed or damaged. The idea behind the view is that strange DNA that does not cause damage, such as a foetus or food, does not and should not trigger an immune response.

The danger signal hypothesis can be schematically represented as in Figure 1.

We propose an extended hypothesis which can be schematically represented as in Figure 2.

The core of the proposed hypothesis is that short term LF EMF exposure, possibly repeated, can produce danger signals that can trigger the immune system activation feedback mechanism in the presence of pathogens. As such, the EMF induced danger signals take the place of the danger signals that would be produced by multiplying pathogens and the damage they cause to cells and tissues. In this way, a timely EMF treatment can avoid the delay given by the time it takes for enough damage
to occur and danger signals to be produced in a normal disease development. Thus, the immune response to pathogens can be advanced in time and damage and a well developed pathogen attack can be avoided.

In a first series of experiments, in vitro common carp head kidney-derived phagocytes were used to determine ROS (Reactive Oxigen Species) production as a measure for immune activation. Exposure to LF EMF signals (250-5000 Hz) at 5 μT or 1,5 mT led to 42% or 33% increase in immune activity, respectively, compared to negative control values. EMF could also additionally stimulate chemically pre-stimulated samples up to 18% (5 μT) or 22% (1,5 mT). Significance of increase in ROS production due to EMF in the total series was: p<0.0001.

In a second series of experiments, in vivo commercial goldfish with infectious disease were used. Groups of fish were housed under equal conditions in at least 4 control tanks and 8 to 16 EMF-exposed tanks.

Without treatment, mortality was about 50% after 18 days, while the treatment at 5 μT reduced it to 20% on average.

Finally, experiments were done with commercial chicken broilers, exposed to Coccidiosis, which is a common infectious disease in poultry, causing major economic losses.

We found that feed conversion, the ratio of the amount of food required to produce a given weight gain in the chicken broilers, was significantly lower for the EMF exposed group with infection than for controls in both experiments. We believe that one explanation for reduced feed uptake in chickens could be less energy spent on developing infections.

Moreover it should be noted that the reduction in feed conversion achieved rivals the best results achieved in comparable trials with preventive antibiotics (now illegal in animal feed in the EU). This indicates that EMF treatment is as effective in suppressing infections and the resulting productive loss in chicken as preventive antibiotics were.

Piglet experiments were performed in a commercial farm as well. Here we used one department as control and another department as test, with 14 meters distance in between. We limited coil size such that the stray fields at the control were calculated to be smaller than 1 nT. At the piglets we achieved 0.4 μT which we hope to increase to 2 to 5 μT in the near future. Results for our early tests showed that the exposed piglets had an 8.6% higher growth per day as % of starting weight than the controls on average over 6 runs, with a standard deviation of 6.3%. Also a 3% better feed conversion was obtained.

Finally, in the Brazilian shrimp industry there is a widespread problem with reduced growth due to inbreeding because of a national ban on importing fresh brood stock for fear of diseases. Because of this we performed a field trial with farmed shrimp in Salvador, Brazil.

In a first run we obtained 50% faster growth from the experimental pond in contrast to that observed in the control pond. The harvest from the treated pond was 808 kg, while the control pond delivered 520 kg, for the same amount of feed employed. The treatment seems to restore normal growth rates and again, much better feed conversion!

Conclusions

This research indicates that this ELF EMF treatment is capable of stimulating the immune system. LF EMF treatment reduces the damage, in terms of intestinal lesions of Coccidiosis infection in broilers. Moreover LF EMF treatment was shown to improve feed conversion up to 12 points, equivalent to some 8% reduced feed uptake for equal growth. Pilot studies with piglets and shrimp growth showed similar feed conversion improvements.

Because of the low field strengths required, and the surprisingly large effects on animal health, the results indicate that practical application with important economic advantages for farmers is possible.

Selected references

Cuppen J.J.M., Wiegertjes G.F., Lobee H.W.J., Savelkoul H.F.J., Elmusharaf M.A., Beynen A.C., Grooten H.N.A. and Smink W. (2007): Immune stimulation in fish and chicken through weak low frequency electromagnetic fields, The Environmentalist, 27, 577-583

Lupke M., Rollwitz J. and Simkó M. (2004) 50 Hz magnetic fields induce reactive oxygen intermediates in human monocytes and in Mono Mac 6 cells. Free Radic. Res. 38, 985-993

Matzinger P. (2002): The danger model: a renewed sense of self. Science 2002;296:301-5.

Simkó M., Droste S., Kriehuber R. and Weiss D.G. (2001): Stimulation of phagocytosis in murine macrophages by 50 Hz electromagnetic fields. Eur. J. Cell Biol. 80, 562-566

Simkó, M. and Mattsson M.O. (2004): Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: possible immune cell activation. J. Cell. Biochem. 93:83-92, 2004.