Pro-inflammatory mediators and neutrophils are increased in synovial fluid from heifers with acute ruminal acidosis

Abstract

Background Acute ruminal acidosis (ARA) is a metabolic disease of cattle characterized by an aseptic synovitis. ARA is the result of an increased intake of highly fermentable carbohydrates that frequently occurs in dairy cattle subjected to high production requirements. In human joint diseases such as rheumatoid arthritis and gout, several pro-inflammatory molecules are increased in the synovial fluid, including cytokines, prostaglandin E 2 (PGE 2 ), metalloproteinases, and neutrophil extracellular traps (NETs). The aim of this study was to identify the presence of proinflammatory mediators and neutrophils in the synovial fluid of heifers with ARA, induced by an oligofructose overload. Five heifers were challenged with an oligofructose overload (13 g/kg BW) dissolved in water. As a control, a similar vehicle volume was used in four heifers. Synovial fluid samples were collected from the tarso-crural joint and PGE 2 , IL-6, IL-1β, ATP, lactate dehydrogenase (LDH), albumin, glucose, matrix metalloproteinase-9 (MMP-9), cellular free DNA, NETs, and serpin B1 were analyzed at 0, 9, and 24 h post treatment. Results At 9 h post oligofructose overload, an increase of IL-1β, IL-6, PGE 2 , serpin B1 and LDH was detected in the joints when compared to the control group. At 24 h, the synovial fluid was yellowish, viscous, turbid, and contained abundant neutrophils. An increase of DNA-backbone-like traps, histone 3 (H 3 cit), aggregated neutrophil extracellular traps ( agg NETs), and serpin B1 were observed 24 h post treatment. Furthermore, albumins, LDH, ATP, MMP-9, IL-6, and IL-1β were increased after 24 h. Conclusions The overall results indicate that IL-1β, IL-6 and PGE 2 , were the earliest proinflammatory parameters that increased in the synovial fluid of animals with ARA. Furthermore, the most sever inflammatory response in the joint was observed after 24 h and could be associated with a massive presence of neutrophils and release of agg NETs. Electronic supplementary material The online version of this article (10.1186/s12917-019-1974-x) contains supplementary material, which is available to authorized users.

Dynamic ROS Production and Gene Expression of Heifers Blood Neutrophil in a Oligofructose Overload Model

“…IL6 plays a complex role related to acute septic shock. A report showed increased levels of IL1β and IL6 in the synovial fluid at 9 and 24 h after OF (13 g/kg) overload in heifers, but not in the plasma (18). In the present study, higher doses of alimentary OF were offered at 17 g/kg of BW; thus, the intensity of the inflammatory response needs further research.…”

“…The level of blood arachidonic acid was elevated in experimentally induced ARA (36). Furthermore, prostaglandins E 2 was also increased in the synovial fluid of heifers with ARA (18). In addition, PMN showed higher gene expression related to arachidonic acid (ALOX5AP and PLA2G4A) in cows fed with high energy diets (8).…”

“…In this current study, the upregulated expressions of CXCL8 and CXCR2 indicates that PMN had stronger chemotaxis. This can cause PMN rapidly recruited to inflamed tissues, such as an influx of PMN into synovial fluid after OF overload in heifers (18). CXCL8 not only played a role in chemotaxis, but also in the release of alkaline phosphatase from secondary granules and the production of ROS by PMN (26).…”

“…OF heifers (n = 6) received 17 g/kg of BW oligofructose dissolved in 2 L/100 kg of BW tap water and the CON heifers (n = 6) received 2 L/100 kg of BW tap water. Blood PMN was isolated for each heifer 0,6,12,18,24,36, 48, 60, and 72 h after administration. PMN was analyzed either by endogenous and phorbol myristate acetate (PMA)-induced ROS production or by quantitative real-time PCR.…”

Laminar Inflammation Responses in the Oligofructose Overload Induced Model of Bovine Laminitis

“…This allows lipopolysaccharide (LPS) to translocate from the digestive tract into the peripheral circulation (17,34,35). Subsequently, free LPS activates systemic inflammatory responses and leads to multiorgan damage, such as rumenitis (36), synovitis (37), and liver impairment (38).…”