Elizabeth Plunkett, Graduate Research Associate, Department of Animal Sciences, The Ohio State University
Inflammation is traditionally defined as "a local response to cellular injury that is marked by capillary dilation, leukocytic infiltration, redness, heat, and pain and that serves as a mechanism initiating the elimination of noxious agents and damaged tissue" (Merriam-Webster). While this definition highlights inflammation's core features, it fails to capture the complexity of this physiological process. To understand inflammation’s role in health and disease, we must acknowledge its nuance and understand its overall goal.
The ultimate goal of the inflammatory process is to restore homeostasis. Although the inflammatory response can be launched to neutralize the initial stimulus, normal tissue may be an unsuspecting casualty during this effort. Inflammation is necessary to create an environment to eliminate the stimulus, but unfortunately, many of the initial host responses also damage host tissue during the process. The absence of effective homeostasis creates an opportunity for sustained inflammation to develop into a chronic inflammatory state and ultimately tissue pathology, resulting in impaired tissue function. It is often tempting to label inflammation as inherently harmful, especially given its historical association with disease. However, this simplification overlooks inflammation’s role in normal physiological processes.
The immune system is complex and plays a key role in coordinating responses to maintain homeostasis. Yet, when it is improperly regulated or repeatedly triggered, inflammation can become maladaptive, resulting in chronic inflammatory states and disease susceptibility. A comprehensive understanding of inflammation requires recognizing its sophistication. While inflammation is frequently studied in pathological contexts, it also plays essential roles in maintaining health. By focusing on its physiological functions, we can better differentiate between beneficial and detrimental inflammatory responses. How we assess inflammation and confront inflammation is approached differently by scientists and veterinarians.
A Scientist’s Perspective:
Inflammation is often exacerbated during critical periods, such as the transition period, when animals are faced with marked physiological changes. The cow gives birth, changes pens, is fed a new ration, and must successfully navigate the biggest homeorhetic adjustment of her lifetime, lactation. The cow is charged to do this for multiple lactations. Additionally, during this time, we often forget about the other physiological adjustments and tissue changes that are occurring (e.g., uterine involution). Dr. Kirby Krogstad, Assistant Professor, Department of Animal Sciences, emphasizes the importance of minimizing stressors during this time. “Every insult during a cow’s life cycle matters, and we need to do everything in our power to not cause repeated insults. By stacking stressors, we are compromising our first line of defense, which makes the job of the second line of defense more challenging,” he said. Continued pressure on initial defenses leads to the introduction of opportunistic pathogens during a time of altered immune function (e.g., transition period), further amplifying inflammatory conditions.
Dr. Krogstad further went on to state, “We must think about the whole system and that inflammation results from different signals.” The stimulatory agent initiating the inflammatory cascade sets the stage for the magnitude of inflammation and subsequent outcomes. For example, E. coli mastitis cases are often acute and severe, while Staph. aureus mastitis is known to be more persistent and chronic. Identifying and understanding how different stimuli initiate inflammatory processes is important, especially when studying chronic inflammation as a pathology. Chronic inflammation is a buzzword in both human and animal sciences, as its impact can lead to unfavorable phenotypes for both. “Chronic inflammation accompanies malfunctioning tissue,” he highlighted. Normal tissue changes can trigger normal physiological inflammation (e.g., leukocyte infiltration of the uterus following calving to initiate uterine involution). In this context, inflammation is a normal and necessary physiology; however, repeated insults, new insults, or tissue maladaptation during this time can create a state of chronic, unresolved inflammation with pathological presentation. Krogstad concluded our discussion by stressing that, “Inflammation is too general a term and we must acknowledge the nuance.” Only when we can identify the constraints of assigning a generalized definition to a process we have yet to fully elucidate, can we progress in our understanding of how to manage it more effectively.
A Veterinarian’s Approach:
Dr. Shaun Wellert, DVM, MS, DACVPM, Assistant Professor, Agricultural Technical Institute, highlights the complexities involved in deciding when to treat and when to let inflammatory processes run their course. “When deciding treatment, we need to think about what the withdrawal periods are, side effects, ease of administration, and whether it is going to help,” he states. Additionally, he emphasized, “animal welfare is a major factor in treatment decision-making.” If the animal is in pain and we know the inflammation occurring will do lasting damage, then treatment is a priority. He also highlighted the importance of being proactive with anti-inflammatory treatments before dehorning, castration, surgery, etc. It is also important to note that the physiological state of the cow (e.g., early or late lactation) can be a driving factor dictating nutrient usage and distribution by the host and the immune system. Therefore, recognizing the stage of life for the cow can affect outcomes and should influence treatment decisions.
The challenge of managing and treating inflammation lies in its context-dependent nature. However, identifying the root cause of why inflammation is occurring is where our resolution resides. “Inflammation is the manifestation of disease, and we need to identify the cause,” he said. Over the years, we have begun to identify many management strategies that reduce stress and inflammation during critical time points in a cow’s life (e.g., gradual weaning of calves). While this area of research is growing each day and drawing more conclusions, we need to be mindful of our interpretation of the results. We have spent too long studying inflammation as a pathology that we have inadvertently removed it from physiology. Inflammation is not inherently a pathology but rather a physiology that has a large pathological potential if left unchecked. Furthermore, Dr. Wellert emphasized that “Inflammation does not happen in a vacuum”, meaning that inflammation does not occur in isolation or without any external influences or context.
Eliminating every possible risk that could cause adverse physiology in a dairy cow is untenable. Sometimes, cows just get sick. But, limiting insult occurrence and duration is a step in the right direction. It is important to note that not all inflammation should be viewed as ‘bad’ inflammation. Inflammation can be a normal physiological process that is necessary for tissue to change and adapt. However, physiological inflammation that occurs during normal tissue changes leaves the host vulnerable to internal and external risks that have the potential to turn inflammation into a pathology. Inflammation can also be the manifestation of disease, meaning it is an indicator or symptom of disease affecting the body, but it is not the disease itself. When identifying treatment strategies, animal welfare should be considered; still, anti-inflammatory treatments often suppress symptoms (e.g., inflammation) and cannot be assumed to ‘fix’ the underlying issue. Targeting the root cause of inflammation should be the ultimate plan for managing the negative outcomes that can result if left unchecked. As our understanding of inflammation evolves, it is essential to reconsider outdated views and embrace the complexity of this physiological process. Only by acknowledging inflammation’s nuance can we leave behind our reductionist mindset and approach dogma and new findings with a questioning, holistic attitude.
The author appreciates the valuable insights shared by Dr. Kirby Krogstad and Dr. Shaun Wellert, faculty at Ohio State University.
Disclaimer: This article is intended to explain and inform readers about some common physiological responses observed in ill lactating cows. It does not constitute veterinary advice or recommendations for treating animals. For specific concerns and treatment plans, please consult a licensed veterinarian.