HESTEFORSK Autologous biological treatments - content and effect on joint inflammation H-16-47-182

Biologic therapies, such as autologous conditioned serum (ACS), are gaining popularity in treating orthopaedic conditions in equine veterinary medicine. Evidence is scarce regarding ACS constituents, and large inter-individual differences in cytokine- and growth factor content have been demonstrated. The objective of the current study was to investigate the potential association between cytokine and growth factor content of ACS and clinical effect in horses with naturally occurring joint-related lameness, as well as investigating the effects of ACS on equine chondcrocytes in vitro. Horses received a standardized ACS treatment course consisting of 3 intra-articular injections administered at 2 week intervals. Lameness evaluation was performed at inclusion and approximately 2 weeks after last treatment; horses were classified as responders when there was no detectable lameness at trot-up and a minimum of 50% reduction in flexion test scores at follow-up. Association between clinical outcome (responders vs. non-responders) and age, lameness score at inclusion, follow-up time and the ACS content of IL-1Ra, IL-1?, IL-1Ra/Il-1 ? ratio, IL-10, IGF-1, TGF-? and TNF-? was determined by regression modelling. Of 20 included horses, 11 responded to treatment whereas 8 did not; one horse was excluded from follow-up analysis due to receiving additional intra-articular medication during the study period. There was considerable inter-individual variability in cytokine/growth factor content of ACS. In the final multivariate logistic regression model, ACS content of IGF-1 and IL-1Ra were significantly associated with clinical response (P = 0.01 and P = 0.03, respectively). In conclusion, the therapeutic benefit of ACS may be related to higher levels of IL-1Ra and IGF-1. Our study corroborates previous findings of considerable inter-individual variability of cytokine- and growth factor content in ACS. Determining ACS levels of IL-1Ra and IGF-1 could be used to identify potential responders vs. non-responders, thereby guiding patient selection prior to initiating treatment.

Våre resultater støtter dagens bruk av AKS i klinisk hestepraksis. Store individuelle forskjeller i innhold av cellesignalstoff i AKS gjør imidlertid effekt av behandling uforutsigbar for den enkelte hest. Videre forskning på metoder som kan måle innhold av cellesignalstoff i forkant av behandlingen vil kunne bidra til å plukke ut hvilke hester som kan dra nytte av behandlingen.

Osteoarthritis (OA), a condition involving inflammation and joint destruction, is a common cause of lameness in horses. There is a need for safe and effective disease-modifying treatments against OA. Autologous biological products such as autologous conditioned serum (ACS) and platelet-rich plasma (PRP) are currently used as intra-articular treatments even though the scientific evidence of positive effects is limited. The products are derived from the patient?s own blood and the complete content and mechanisms of action are not fully understood. The purpose of this project is to define the individual components of the preparations in vivo and characterise their effects on inflamed articular cartilage in a well-established in vitro system. Additionally, individual differences and different methods of preparations will be studied. This will increase the scientific knowledge about the blood-derived products and guide recommendations for their use. The composition of ACS and PRP will be explored in vivo and the effects on articular cartilage will be studied in vitro. Established methods for in vivo as well in vitro studies are available (Fjordbakk et al. 2015, Svala et al. 2015, Löfgren's thesis 2016). Commercial kits for preparation of ACS and PRP commonly used in equine practice will be used and thereby yield clinically relevant results.