PRRSV and Mycoplasma hyopneumoniae: tylvalosin and the role of cytokine responses

Porcine respiratory disease is exacerbated by  pro-inflammatory cytokine-mediated inflammation

• Porcine respiratory disease is often treated with antimicrobials
• Tylvalosin, a macrolide antibiotic, has bactericidal activity against Mycoplasma hyopneumoniae (M. hyo)
• Tylvalosin also has an immunomodulatory effect, damping down the cytokine response, and this may be responsible for tylvalosin’s beneficial effects against pathogens like PRRSV

The immunomodulatory activitiy of tylvalosin means that it has a potential additive effect in the treatment of respiratory infections in pigs, which goes beyond its antimicrobial activity. A recent study looked at the effects of oral tylvalosin on disease caused by porcine reproductive and respiratory syndrome (PRRS) alone in sows, or in combination with M. hyo in piglets, with a particular focus on tylvalosin’s immunomodulatory benefits.

Understanding Porcine Respiratory Disease Complex (PRDC)

• PRDC is a multifactorial condition
• Primary pathogens include porcine reproductive and respiratory syndrome virus (PRRSV) and M. hyo
• Management and environmental factors are also involved
• Respiratory disease is more severe when a combination of pathogens is involved
• Both M. hyo and PRRSV can negatively alter immunoregulatory cytokines
• PRDC is exacerbated by pro-inflammatory cytokinemediated inflammation, also known as a ‘cytokine storm’

Understanding cytokines

• Cytokines are proteins that regulate immune and inflammatory responses
• They play an important role in the pathogenesis of many clinical conditions, including PRDC
• Some cytokines are pro-inflammatory…
• … while some cytokines play a role in damping down the immune response
• Imbalances between proinflammatory and antiinflammatory cytokines can result in more severe clinical signs and poorer clinical outcomes

Tylvalosin and the cytokine response: results of a 2023 study1

The effect of a water-soluble formulation of tylvalosin (Aivlosin® 625mg/g granules) on disease caused by PRRSV and M. hyo was investigated. The two-part study comprised a PRRSV challenge model in pregnant sows and a dual PRRSV and M. hyo challenge model in piglets. Cytokine levels increased after PRRSV challenge both locally (uterus and lungs) and systemically (serum).

In the PRRSV challenge study in pregnant sows, tylvalosin:

• reduced serum levels of cytokines IL-8, IL-12, TNFα and GM-CSF
• reduced uterine levels of IL-8

In the dual challenge study in piglets, tylvalosin:

• reduced serum levels of 16 cytokines, including IL-8 and TNFα
• reduced lung levels of IL-8, IL-10 and IL-12
• increased serum IFNα The study concluded that tylvalosin had a highly significant immunomodulatory effect on multiple cytokines in both sows and piglets.

TNFα and IL-8: a closer look

Tylvalosin in the face of cytokines TNFα and IL-8 were of particular interest, as they were expressed less in tylvalosin treated groups, both systemically (serum) and locally (uterus or lungs). Previous studies have shown that they are produced in the early stages of infection, and along with other cytokines, result in stimulation of local and systemic inflammatory responses.²

TNFα is a cell-signalling and regulatory cytokine that has been positively correlated with the severity of porcine respiratory disease.2,3 It can have pro-inflammatory effects or antiinflammatory (anti-viral) effects and it may have a role in the pulmonary defences against PRRSV.4,5 IL-8 is a pro-inflammatory cytokine that is secreted after bronchiolar epithelial cell death (apoptosis). Aberrant production of both IL-8 and TNFα could lead to damage to healthy tissue.

Improving PRRSV outcomes: the role of IFNα

Some cytokines, including IFNα, play a role in damping down the immune response. Pigs have been shown to generate a poor IFNα response following PRRSV infection and it is suggested that increasing this response may lead to improved PRRSV outcomes.

Tylvalosin in the face of cytokines

Cases of porcine respiratory disease are often treated with antibiotics. With proven efficacy against respiratory pathogens, including M. hyo, and low, effective therapeutic dose, tylvalosin use aligns with the responsible prescribing of antibiotics. Furthermore, the current study showed that tylvalosin also had a highly significant immunomodulatory effect on multiple cytokines in both sows and piglets challenged with M. hyo and/or PRRSV. This immunomodulation, in addition to antibiotic activity, is likely to have reduced the overall severity of the disease.

References

1. Lopez Rodriguez, A.L., et al. Effects of a water-soluble formulation of tylvalosin on disease caused by porcine reproductive and respiratory syndrome virus alone in sows or in combination with Mycoplasma hyopneumoniae in piglets. BMC Vet Res. 2023 Feb 1;19(1):31
2. Vissche, A.H., et al. Disease incidence and immunological traits for the selection of healthy pigs A review. Vet. Q. 2002;24:29–34
3. Boddicker, N.J., et al. Validation and further characterization of a major quantitative trait locus associated with host response to experimental infection with porcine reproductive and respiratory syndrome virus. Anim. Genet. 2014;45:48–58
4. Gol, S., et al. Expression profiling of the GBP1 gene as a candidate gene for porcine reproductive and respiratory syndrome resistance. Anim. Genet. 2015;46:599–606.
5. Hess, A.S., et al. Comparison of host genetic factors influencing pig response to infection with two North American isolates of porcine reproductive and respiratory syndrome virus. Genet. Sel. Evol. 2016;48:43
6. Jansen, T., et al. Assessing the Value of Antibiotics on Farms: Modeling the Impact of Antibiotics and Vaccines for Managing Lawsonia intracellularis in Hog Production. Front Vet Sci. 2019 18;6:364
7. Yeske, P. 2016. Mycoplasma hyopneumoniae elimination, 2016 AASV Annual Meeting Proceedings, pg. 376-380. https:// www.aasv.org/library/swineinfo/item

To discuss the management of porcine respiratory disease on your farm, or to learn more about the responsible use of tylvalosin, contact our technical services team by emailing enquiries@ecoanimalhealth.com