Unraveling a mystery of SINS and its potential tie to endotoxins

Swine Inflammatory and Necrotic Syndrome (SINS) is a disease affecting pigs and is characterized by fever, inflammation, and necrosis in various organs. The causes of SINS are not fully understood, but factors such as viral infections, genetics, and environmental stressors may play a role. Similar to endotoxins, SINS is believed to be caused by a systemic inflammatory response and involves the release of pro-inflammatory mediators such as cytokines. Understanding the causes of SINS is crucial in reducing the incidence and severity of the syndrome.

Signs and symptoms

The symptoms of swine inflammatory and necrotic syndrome (SINS) can vary depending on the stage and severity of the disease, but some common symptoms include:

  • Fever: Pigs with SINS often have a high fever that can last for several days.
  • Inflammation: SINS is characterized by inflammation in various organs of the pig’s body, especially the lungs, liver, and spleen.
  • Necrosis: Necrosis, or death of tissue, is another characteristic of SINS and can be seen in the organs affected by inflammation.
  • Respiratory symptoms: SINS can cause respiratory signs, such as coughing, difficulty breathing, and an increased breathing rate/panting.
  • Diarrhea: Some pigs with SINS may also have diarrhea.
  • Loss of appetite: Pigs with SINS may have a reduced appetite, which can lead to weight loss.
  • Depression: Pigs affected by SINS may appear depressed and lethargic.
  • Dehydration: Due to the fever and diarrhea, pigs may become dehydrated.

It is important to note that these symptoms can also be caused by other diseases, so a veterinarian should be consulted for a proper diagnosis.

Likely culprits of SINS

It was initially thought that inflammation and necrosis are exclusively caused by biting and mechanical irritation, however, different studies are demonstrating that there are more causes. According to reviews on the pathology of SINS, three main observations support the view that SINS is primarily an endogenous (internal) disease, even though it may be modified by production practices and other mechanical stressors.

  1. Occurrence in distal (away from the core) body parts such as the tail, teats, and claws
  2. Evidence that SINS can be expressed before birth
  3. Proof that inflammation originating from the blood vessels is present before birth. Studies (that control against biting and mechanical irritation) have shown piglets can still develop SINS

Currently, SINS is believed to be caused by a combination of factors, with one endogenous factor expected to be exposure to endotoxins. Normally present in the gastrointestinal tract (GIT) of swine, endotoxins are toxic substances found in the cell walls of gram-negative bacteria (Figure 1). Gram-negative bacteria are part of the normal gastrointestinal microbiota of healthy animals, however, under certain stress conditions or production phases (change of diets) their presence in the gastrointestinal tract is increased. With a higher concentration of gram-negative bacteria, there is an increase in the presence of endotoxins (also known as lipopolysaccharides or LPS) released into the body when the bacteria die or the cell walls are damaged. Mycotoxins (DON and similar substances) disintegrate the tight junctions of the blood–intestinal barrier and can increase LPS uptake in pigs.

Structure of an endotoxin

Figure 1: Typical endotoxin structure. Lipid A is embedded in the outer membrane of gram-negative bacteria

One theory is that exposure to high levels of endotoxins can cause inflammation and damage to the organs of the pig’s body, leading to the symptoms of SINS. This is because endotoxins can trigger the release of pro-inflammatory mediators and cause a systemic inflammatory response leading to multiple organ failure. It should be noted that the relationship between SINS and endotoxins is not fully understood yet and more research is needed to understand and confirm the exact mechanism.

Similar modes of action

It is believed that SINS is caused by a systemic inflammatory response, which is characterized by the release of pro-inflammatory mediators such as cytokines. Cytokines are a group of small proteins that are involved in the regulation of the immune response. Some of the pro-inflammatory cytokines that have been associated with SINS include tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). All of these potent pro-inflammatory cytokines are involved in the regulation of the immune response and are known to play roles in the development of inflammation and tissue damage associated with various diseases. Since endotoxins trigger a proinflammatory reaction mediated through some of the same cytokines associated with SINS, it seems to confirm the hypothesis that endotoxins are one of the factors involved in SINS.

Since there is evidence of the association of SINS with the presence of endotoxins, reducing the impact of endotoxins in pigs may contribute to reducing the incidence and virulence of SINS. Studies performed at the University of Ghent have demonstrated the capacity of some toxin binders to capture endotoxins in the gastrointestinal tract, thus stopping their action in the intestinal epithelium and limiting adsorption to the bloodstream. The study demonstrated the effect of the toxin binder in reducing the production of inflammatory cytokines. Precisely the same mediators associated with SINS as described before.

In the study, the authors compared the effect on the production of cytokines by injection of endotoxins with or without the addition of the toxin binder. Based on a model of Vandenbroucke et al., 2011, the ex vivo model was intestinal loops of live piglets. The study consisted of surgery on two female piglets at 5 weeks of age. Intestinal loops 8 cm long of jejunum were used as experimental units (Figure 2).

Set-up of the toxin binder trial against endotoxins

Figure 2: In two 5-week-old piglets, 3 intestinal loops per treatment of 8 cm were produced at the level of the jejunum. Different
conditions were then injected directly in the intestinal loop and a biopt of each look was taken to determine endotoxin binding

The data from this trial (Figures 3 & 4) proved that the toxin binder was capable of reducing cytokine production that results from endotoxin activation of the inflammatory response. As mentioned before, the cytokine studied in this trial were very similar to those that have been associated with SINS.

Piglet APiglet B
1) Control loops with no LPS induced1) Control loops with no LPS induced
2) 200,000 EU LPS2) 200,000 EU LPS
3) 200,000 EU LPS + HSCAS (0.3% w/v)3) 200,000 EU LPS + HSCAS (0.3% w/v)
4) HSCAS (0.3% w/v)

The inflammatory cytokines measured via qPCR analysis were IL-1β, IL-6, and MCP-1.

Figures 3&4: When the toxin binder (HSCAS) was included, the production of inflammatory cytokines were decreased

SINS is known to result from a range of factors, including stress, production practices, genetics, and endogenous causes. Inflammatory cytokines play a role in the pathogenicity of SINS, as they mediate the action of both SINS and LPS (endotoxins). This relationship supports the theory that LPS is one of the causes of SINS. By using toxin binders to regulate LPS action, we can mitigate the severity of SINS.

Your Agrimprove expert

Do you have a question or want personalized advice? Your Agrimprove expert is willing to help. Reach out directly or request to be contacted at your convenience.

Josep Garcia-Sirera
Product manager

Stay up-to-date

Would you like to be kept informed of our latest developments? Register here and stay up to date.

I'm interested in(Required)

Agrimprove can store and use my personal information to respond to my request, as stipulated in the privacy policy.

This field is for validation purposes and should be left unchanged.