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Published on: September 4, 2012
Administration of recombinant human interleukin 1 receptor antagonist during endotoxin-induced mastitis in cows
1Metabolic Diseases and Immunology Research Unit, National Animal Disease Center, USDA, Ames, IA 50010, USA.
Insights
Interleukin 1 (IL-1) plays a role in mastitis, but its receptor antagonist (IL-1ra) did not reduce inflammation or improve cow productivity. This suggests IL-1 may not be critical for mastitis, or the treatment was ineffective.
Area of Science:
- Veterinary Immunology
- Bovine Pathology
- Inflammatory Mediators
Background:
- Mastitis is a significant concern in dairy cattle, leading to economic losses.
- Interleukin 1 (IL-1) is recognized as a key inflammatory mediator in mastitis.
- Understanding IL-1's role and potential therapeutic targets is crucial for disease management.
Purpose of the Study:
- To investigate the role of IL-1 in bovine mastitis.
- To evaluate the therapeutic efficacy of recombinant human IL-1 receptor antagonist (IL-1ra) in treating mastitis.
Main Methods:
- Cows were induced with intramammary lipopolysaccharide (LPS) to model mastitis.
- Experimental group received IL-1ra infusions prior to and after LPS administration.
- Whey and milk samples were analyzed for cytokines, somatic cell counts, and milk composition.
- Systemic effects like fever and cortisol levels were monitored.
Main Results:
- LPS infusion increased IL-1 and tumor necrosis factor bioactivity in milk.
- Increased vascular permeability and neutrophil infiltration were observed.
- IL-1ra administration significantly reduced IL-1 bioactivity in milk.
- However, IL-1ra did not alter local inflammation, systemic responses, or milk yield.
Conclusions:
- IL-1 may not mediate mastitis effects within the milk compartment.
- IL-1 might not be a critical factor in the overall mastitic response.
- The administration route of IL-1ra may limit its efficacy in blocking IL-1's receptor interactions.
Abstract:
The role of interleukin 1 (IL-1) as an inflammatory mediator during mastitis and the therapeutic effect of recombinant human IL-1 receptor antagonist (IL-1ra) for bovine mastitis was studied. Cows were intramammarily infused with lipopolysaccharide (25 micrograms) in 1 mammary gland. Half the cows also received infusions of 5 mg of IL-1ra into the same mammary gland just prior to endotoxin infusion and 4, 8, and 12 hours later. After endotoxin infusion, tumor necrosis factor and high IL-1 bioactivity were detected in whey from infused glands. Vascular permeability changes and neutrophil accumulation in milk paralleled the appearance of cytokines. A systemic reaction, characterized by pyrexia and an increase in blood cortisol concentration, also were observed. Milk yield was inhibited and milk composition was altered in infused and noninfused glands. The increase in IL-1 bioactivity in milk after endotoxin infusion was almost completely prevented in glands receiving IL-1ra. However, IL-1ra had no effect on local inflammation, systemic reaction, or impairment in productive performance. These results indicate that IL-1 does not mediate its effect within the milk compartment, and suggest either that IL-1 is not critical to the mastitic response or that intramammary infusion of IL-1ra does not place the antagonist where IL-1 interacts with its receptor.

