In the European Union, the use of high doses of zinc for weanling piglets will be prohibited in June 2022. Although the “medical zinc” efficiently reduces post-weaning diarrhea (PWD), it also contributes to antibiotic resistance in microbes, and accumulates into the environment. At the moment, the pig industry is actively seeking for alternatives to high doses of zinc, with a similar capacity to reduce PWD but without concerns regarding environmental accumulation or antibiotic resistance. It is noteworthy that the mechanism-of-action of high doses of zinc in piglets has never been fully elucidated, but anti-inflammatory and antimicrobial mechanisms are involved.

Hankkija’s Progres®, the only source of coniferous resin acids for farm animal feeds, has previously been proven to significantly reduce PWD and post-weaning mortality, and to improve the production performance of piglets (Uddin et al., 2021). Coniferous resin acids protect the intestinal epithelium against collagen degradation by inflammation-associated endogenous enzymes. Dietary resin acids also reduce the density of proinflammatory T-cells in small-intestinal epithelium. However, immunomodulatory capacity of resin acids in piglets has not been extensively studied.

For resin acids in animal feeding, there is no risk for environmental accumulation, because resin acids are readily degraded by the natural microbiome of all soils. Neither do they contribute to the antibiotic resistance problems because they do not have antimicrobial action against the natural microbial community of animal gut.

Materials and methods

The present study aimed to compare dietary resin acids and medical doses of zinc as immunomodulators for piglets. For inducing a disease-like condition, piglets were twice challenged with intraperitoneal E. coli lipopolysaccharide (LPS) which induces fever and diarrhea in piglets. The same LPS response is created naturally during PWD in piglets, when LPS from gut lumen enters the bloodstream. The healthy control animals in this trial were injected with a saline solution (PBS) to control for the effect of injection.

Progres® Liquid contains 9% resin acids in a fatty acid matrix. In the present study, a resin acid concentrate (RAC) was used, with 40% coniferous resin acids attached into a wheat-based carrier. The resin acid mixture is the same as in Progres Liquid.

For the experiment, 48 piglets (26 days old) were randomized into four treatments:

  1. Non-challenged group with control diet (Healthy control)
  2. LPS-challenged group with control diet (Negative control)
  3. LPS-challenged group with medical zinc 2500 mg ZnO/kg diet (Zinc)
  4. LPS-challenged group with 200 mg RAC/kg diet (RAC)

Piglets were housed in pens of six piglets, 2 pens/treatment. They were fed ad libitum for 21 days with the treatment diets, and subjected to LPS or PBS injections on d 7 and 21.

Blood samples were taken at 1.5 hour (h) and 3 h after each infection. Blood serum samples were also collected at one time point (d14) between LPS challenges to study the effect of dietary treatments on the immunological status of nonchallenged animals. Serum immune biomarkers including Interleukin (IL)-1β IL-4, IL-6, IL-8, IL-10, IL-12, Tumor necrosis factor (TNF)-α, Interferon (IFN)-α and IFN-γ were measured.

Data were analyzed by two-way ANOVA using time and treatment as factors. Weekly growth performance and rectal temperature at various times were recorded. Rectal temperature reflected activation of the immune system by LPS.


The results, now published in the peer-reviewed journal Frontiers in Animal Science, showed that both medical zinc and RAC stimulate a number of cytokines after the LPS injection. In contrast, on day 14 with no LPS challenge, all the cytokines of all treatments were at baseline levels.

Of the array of cytokines measured, some responded clearly to the treatments while some others did not. Interleukins IL-1β, IFN- α, IFN-γ and IL-4 remained unresponsive while effects were found for IL-6, IL-8, IL-10, IL-12, and TNF-α.

One of the cytokines, IL-10, has a specific anti-inflammatory role. Dietary RAC had a strong up-regulating effect on serum IL-10 -concentration while Zinc did not increase the levels of this cytokine. It is possible that the anti-inflammatory responses of resin acids are partly mediated via IL-10.

The proinflammatory mediator TNF-α was equally up-regulated by Zinc and RAC. Interleukins IL-6, IL-8 and IL-12 responded more strongly to RAC than Zinc.


In conclusion, both RAC and high dose of zinc modulate the immunological response to LPS in piglets, but RAC induces a stronger anti-inflammatory response than zinc. Neither of these dietary components caused an up-regulation of cytokines without the presence of LPS challenge.

Based on the results of the present study and the study by Uddin et al. (2021), a resin acid -based product Progres® can be suggested to replace medical doses of zinc in weanling piglet diets.


Guan, X., Santos, R., Kettunen, H., Vuorenmaa, J. and Molist, F. (2021) Effect of resin acid and zinc oxide on immune status of weaned piglets challenged with E. coli lipopolysaccharide. Frontiers in Veterinary Science.

Uddin, M.K., Hasan, S., Mahmud, M.R., Peltoniemi, O. and Oliviero, C. (2021) In-feed supplementation of resin acid-Eeriched composition modulates gut microbiota, improves growth performance, and reduces post-weaning diarrhea and gut inflammation in piglets. Animals 11: 2511.