Cow 459 is dry, but she has a hard quarter this morning. Following further investigation, she is confirmed with a case of clinical mastitis.

This isn’t an unusual situation. Research shows that the rate of new intramammary infections is significantly higher in the dry period than during lactation. The average rate of new infections in untreated dry cows is expected to be between 8 and 12 percent of quarters, according to data from the NMC (formerly the National Mastitis Council).

Therefore, dry cow antibiotic therapy remains the recommended best-practice to prevent mastitis infections from developing during this period, particularly the early dry period. However, with heightened public concerns about antibiotic usage and potential implications for food safety and public heath (real or perceived), the hunt is on for new and improved tools to deal with this disease that has a $2 billion annual price tag.

Several studies have shown encouraging results for immunotherapy treatments.

Q: What is the mode of action for these approaches?

A: The field of immunotherapy seeks to stimulate the cow’s own immune response against infections. One area of exploration is by the addition of specific cytokines — which are proteins released by cells that impact cell interactions — to the udder at dry-off.

Enhancing the immunity of a diminished mammary gland system may provide an effective barrier against new intramammary infections during periods of increased susceptibility to disease, such as the case during the dry period, says Daniela Resende-Bruno, microbiologist at the Texas Veterinary Medical Diagnostic Laboratory in Amarillo, Texas.

This is not a new idea; rather, scientists have been looking to cytokines as a mastitis defense tool for a while. Results have been promising, but challenges remain, too.

In research published in the Journal of Dairy Science in 1995, researchers at Ohio State University found that the addition of a cytokine, Interleukin 2, to a regular dry cow antibiotic that targeted Staphlococcus aureus enhanced the effectiveness of the treatment. However, there were some negative side effects, particularly in the form of abortion for 7.5 percent of cows that received cytokine in this experiment.

In 2008, New Zealand researchers investigated the potential of infusing recombinant bovine interleukin-1B in the udder as a tool to reduce infections caused by Streptococcus uberis in the dry period.

Their results, published in the April 2008 journal Veterinary Research Communications, show that this cytokine did indeed lessen the number of infections due to this pathogen. But, high somatic cell levels masked the full benefit of the procedure.

Q: What are some other areas of immunotherapy under exploration?

A: Sugar, specifically a polysaccharide known as Poly-x that occurs naturally in the cell walls of certain yeasts, has been shown to be effective against mastitis infections by USDA-Agricultural Research Service scientists in Beltsville, Md.

This method works by mobilizing bacteria-killing white blood cells early in the dry period. The result is an increase in the activity of immune cells, especially in the first five days of the dry period.

Since these cells were primed and ready to fight off infections, cows receiving the treatment had fewer cases of mastitis.

Proteomics is another new tool. It’s used to study the dynamic interactions between an immune system whose goal is to detect and destroy pathogens and a microbe that must evade the immune system to survive. Unlike other methodologies that analyze a few proteins at a time, proteomics can analyze thousands of proteins in a single experiment.

This ability enables researchers to demonstrate how cells dynamically respond to changes in their environment. Therefore, a goal of proteomics is to identify new and potentially unexpected changes in protein expression, interaction or modification as a result of an experimental treatment.

This tool can be used for a myriad of diseases and functions, but in terms of mastitis, researchers are using this approach to better understand and prevent infections from Escherichia coli.

Q: Is there a connection between nutrition and immune function?

A: Yes. Nutrition can have significant effects on a cow’s immune system, thereby affecting the infection rate and severity of mastitis, says Bill Weiss, Ohio State University dairy nutritionist.

Long-term research repeatedly shows that you need to prevent cows from becoming too fat in late lactation and the dry period, avoid large decreases in dry matter intake during the pre-partum period, and promote a rapid increase in energy intake after calving.

In addition, there’s compelling data that emphasize the need to pay attention to calcium and antioxidant nutrients in dry-cow rations because they can enhance or diminish immunity.

“Available data clearly show that preventing subclinical and clinical milk fever (hypocalcemia) will reduce the prevalence of mastitis in early lactation,” says Weiss.

That’s because calcium is needed for muscle contractions, and if a cow experiences hypocalcemia, her teat sphincters may not contract as quickly or completely. This opens her up to increased risk of bacterial invasion. Cows with milk fever also have higher concentrations of plasma cortisol than normal cows; cortisol suppresses immune function. If that weren’t enough, the calcium status of monocytes (white blood cells) is impaired in cows with milk fever, reducing the ability of these cells to function properly, says Weiss.

Lastly, there’s a connection between antioxidant nutrients and a cow’s ability to fight off infections. When a mammary gland becomes infected, substantial amounts of free radicals are produced during the cows’ inflammatory response, explains Weiss. “When adequate antioxidants are present, free radicals are kept in check, which increases the lifespan of certain immune cells.” If this balance gets out of whack, and antioxidant capacity is limited, the lifespan of those immune cells is reduced and the infection can become established or the severity of the infection can increase.

Research shows that feeding adequate levels of trace minerals and vitamins are essential to success in this area. Repeated studies show that supplemental vitamin E and/or selenium reduces prevalence and severity of mastitis. Other key nutrients include vitamin A, beta-carotene, copper and zinc.

Glossary of terms

The area of immunotherapy features several terms that may be unfamiliar. Here are some definitions that you need to know.

Cytokine: A small protein released by cells that has a specific effect on the interactions between cells, communications between cells or the behavior of cells. Cytokines include the interleukins, lymphokines and cell signal molecules, such as tumor necrosis factor and the interferons, which trigger inflammation and respond to infections.

Immunotherapy: A medical term defined as the treatment of disease by inducing, enhancing, or suppressing an immune response. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. Immunotherapies designed to reduce, suppress or more appropriately direct an existing immune response are classified as suppression immunotherapies. The active agents of immunotherapy are collectively called immunomodulators.

Monocyte: A type of white blood cell that responds to inflammation signals from the body.

Proteomics: The study of protein expression, protein-protein interaction or protein modification.