Metabolic Diseases of Ruminants, An Issue of Veterinary
Clinics Food Animal Practice
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Metabolic Diseases of Dairy Cattle
Contributors
CONSULTING EDITOR
ROBERT A. SMITH, DVM, MS
Diplomate, American Board of Veterinary Practitioners; Veterinary Research and
Consulting Services, LLC, Greeley, Colorado
EDITOR
THOMAS H. HERDT, DVM, MS
Diplomate, American College of Veterinary Nutrition; Diplomate, American College of
Veterinary Internal Medicine; Professor, Department of Large Animal Clinical Sciences,
College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
AUTHORS
MICHAEL S. ALLEN, PhD
University Distinguished Professor, Department of Animal Science, Michigan State
University, East Lansing, Michigan
DONAGH P. BERRY, PhD
Principal Research Officer, Animal Genetics, Teagasc, Moorepark Dairy Production
Research Centre, Fermoy, County Cork, Ireland
GIUSEPPE BERTONI
Faculty of Agriculture; Former Head, Institute of Zootechnic, Professor, Università
Cattolica del Sacro Cuore, Piacenza, Italy
JENNE D. DE KOSTER, DVM
PhD Student, Department of Reproduction, Obstetrics and Herd Health, Faculty of
Veterinary Medicine, Ghent University, Merelbeke, Belgium
PETER J. DEGARIS, BVSc (Hons), PhD
Tarwin Veterinary Group, Leongatha, Victoria, Australia
TODD F. DUFFIELD, DVM, DVSc
Professor, Department of Population Medicine, Ontario Veterinary College, University of
Guelph, Guelph, Ontario, Canada
NIC C. FRIGGENS, PhD
Head of INRA, AgroParisTech Research Unit 791, Modélisation Systémique Appliquée aux
Ruminants, Paris, France
JESSICA L. GORDON, BS, DVM
Department of Population Medicine, Ontario Veterinary College, University of Guelph,
Guelph, Ontario, Canada
JANE K. KAY, PhD
Team Leader, Dairy Cow Nutrition, DairyNZ, Hamilton, New Zealand
iv Contributors
IAN J. LEAN, BVSc, DVSc, PhD, MANZCVS
SBScibus, Camden, New South Wales, Australia
STEPHEN J. LEBLANC, BSc, DVM, DVSc
Associate Professor, Department of Population Medicine, Ontario Veterinary College,
University of Guelph, Guelph, Ontario, Canada
JUAN J. LOOR, PhD
Associate Professor, Animal Sciences and Nutritional Sciences, University of Illinois,
Urbana, Illinois
JESSICA A. MCART, DVM, PhD
Assistant Professor, Department of Clinical Sciences, Colorado State University,
Fort Collins, Colorado
DARYL V. NYDAM, DVM, PhD
Associate Professor, Department of Population Medicine and Diagnostic Sciences,
Veterinary Medical Center, Cornell University, Ithaca, New York
GARRETT R. OETZEL, DVM, MS
Diplomate, American College of Veterinary Nutrition (Honorary); Associate Professor,
Food Animal Production Medicine Section, Department of Medical Sciences, School of
Veterinary Medicine, University of Wisconsin–Madison, Madison, Wisconsin
GEERT OPSOMER, DVM, PhD, Msc
Diplomate, European College of Animal Reproduction; Diplomate, European College of
Bovine Health Management; Professor, Department of Reproduction, Obstetrics and
Herd Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
PAULA A. OSPINA, DVM, MPH, PhD
Senior Lecturer, Department of Animal Science, Cornell University, Ithaca, New York
THOMAS R. OVERTON, PhD
Associate Professor, Department of Animal Science, Cornell University, Ithaca, New York
PAOLA PIANTONI, Veterinaria, MS
Graduate Research Assistant, Department of Animal Science, Michigan State University,
East Lansing, Michigan
WILLIAM RAPHAEL, BVSc, MS
Diplomate, American Board of Veterinary Practitioners (Dairy); Diplomate, American
College of Veterinary Preventive Medicine; Department of Large Animal Clinical Sciences,
College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
JOHN R. ROCHE, PhD
Principal Scientist, Animal Science, DairyNZ, Hamilton, New Zealand
LORRAINE M. SORDILLO, MS, PhD
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan
State University, East Lansing, Michigan
TRACY STOKOL, BVSc, PhD
Diplomate; American College of Veterinary Pathologists, Associate Professor,
Department of Population Medicine and Diagnostic Sciences, Cornell University,
Ithaca, New York
Contributors v
ERMINIO TREVISI, PhD
Faculty of Agriculture, Institute of Zootechnic, Assistant Professor, Università Cattolica
del Sacro Cuore, Piacenza, Italy
ROBERT VAN SAUN, DVM, MS, PhD
Diplomate, American College of Theriogenology; Diplomate, American College of
Veterinary Nutrition; Professor, Department of Veterinary and Biomedical Sciences,
Pennsylvania State University, University Park, Pennsylvania
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Metabolic Diseases of Dairy Cattle
Contents
Preface: Metabolic Diseases of Dairy Cattle xi
Thomas H. Herdt
Significance of Metabolic Stress, Lipid Mobilization, and Inflammation on Transition
Cow Disorders 267
Lorraine M. Sordillo and William Raphael
The incidence and severity of disease in cows is greatest during the tran-
sition period, when immune functions are impaired. Intense lipid mobiliza-
tion is associated with both metabolic and infectious diseases in the
transition cow. Significant increases in plasma nonesterified fatty acids
contribute to oxidative stress and uncontrolled inflammatory responses.
A dysfunctional inflammatory response is the common link between met-
abolic and infectious diseases around the time of calving. Intervention
strategies that can reduce lipid mobilization may improve inflammatory re-
sponses and reduce the economic losses associated with health disorders
during the transition period.
Metabolic Control of Feed Intake: Implications for Metabolic Disease of Fresh Cows 279
Michael S. Allen and Paola Piantoni
The objective of this article is to discuss metabolic control of feed intake in
the peripartum period and its implications for metabolic disease of fresh
cows. Understanding how feed intake is controlled during the transition
from gestation to lactation is critical to both reduce risk and successfully
treat many metabolic diseases.
Insulin Resistance in Dairy Cows 299
Jenne D. De Koster and Geert Opsomer
Glucose is the molecule that drives milk production, and insulin plays a piv-
otal role in the glucose metabolism of dairy cows. The effect of insulin on
the glucose metabolism is regulated by the secretion of insulin by the pan-
creas and the insulin sensitivity of the skeletal muscles, the adipose tissue,
and the liver. Insulin resistance may develop as part of physiologic (preg-
nancy and lactation) and pathologic processes, which may manifest as
decreased insulin sensitivity or decreased insulin responsiveness. A
good knowledge of the normal physiology of insulin is needed to measure
the in vivo insulin resistance of dairy cows.
Assessing and Managing Body Condition Score for the Prevention of Metabolic
Disease in Dairy Cows 323
John R. Roche, Jane K. Kay, Nic C. Friggens, Juan J. Loor, and Donagh P. Berry
Body condition score (BCS) is an assessment of a cow’s body fat (and
muscle) reserves, with low values reflecting emaciation and high values
equating to obesity. The intercalving profile of BCS is a mirror image of
the milk lactation profile. The BCS at which a cow calves, her nadir
viii Contents
BCS, and the amount of BCS lost after calving are associated with milk
production, reproduction, and health. Genetics, peripartum nutrition, and
management are factors that likely interact with BCS to determine the
risk of health disorders.
Energy and Protein Nutrition Management of Transition Dairy Cows 337
Ian J. Lean, Robert Van Saun, and Peter J. DeGaris
The aims of this article are to briefly review some of the underlying physi-
ology of changes that occur around calving, examine the potential to con-
trol the risk of disease in this period, increase milk production, and improve
reproductive performance through better nutritional management. Practi-
cal guidelines for veterinarians and advisors are provided.
Mineral and Antioxidant Management of Transition Dairy Cows 367
Ian J. Lean, Robert Van Saun, and Peter J. DeGaris
Transition management needs to be fully integrated to be effective. We
discuss and demonstrate this concept in the context of a study that
used these principles. The roles of calcium, magnesium, phosphorus
and dietary anion cation difference in influencing the pathophysiology
and incidence of hypocalcemia are highlighted. Recent understandings
of the pivotal role of skeleton in metabolism are reviewed. Micronutrient
mineral and vitamin needs are addressed in the context of exposure of
periparturient cattle to oxidative stress and inflammatory disorders. This
article provides a series of practical approaches to improving transition
diets.
Using Nonesterified Fatty Acids and b-Hydroxybutyrate Concentrations During the
Transition Period for Herd-Level Monitoring of Increased Risk of Disease and
Decreased Reproductive and Milking Performance 387
Paula A. Ospina, Jessica A. McArt, Thomas R. Overton, Tracy Stokol, and
Daryl V. Nydam
Dairy cows visit a state of negative energy balance (NEB) as they transition
from late gestation to early lactation. At the individual level, there are
several metabolic adaptations to manage NEB, including mobilization of
nonesterified fatty acids (NEFA) from body fat reserves and glucose spar-
ing for lactogenesis. Based on current pen-level feeding and management
practices, strategies to minimize excessive NEB in both the individual and
herd should focus on herd-level testing and management. This article
reviews strategies for testing and monitoring of excessive NEB at the
herd level through individual testing of 2 energy markers: NEFA and
b-hydroxybutyrate.
Use of the Liver Activity Index and Other Metabolic Variables in the Assessment of
Metabolic Health in Dairy Herds 413
Giuseppe Bertoni and Erminio Trevisi
The usefulness of the metabolic profile in dairy cows has been questioned
because of poor standardization of procedures, high cost of analysis, and
perceived inefficiency of the approach. Composite indices based on mul-
tiple variables, namely the Liver Activity Index and the Liver Functionality
Contents ix
Index, which consider the pattern of changes of some negative acute-
phase proteins in the first month of lactation, appear promising in the
assessment of metabolic health status and the prediction of lactational
and reproductive performance. The application of such indices depends
on their reliability and on making them practical and economical regarding
test cost and number of sampling points required.
Ketosis Treatment in Lactating Dairy Cattle 433
Jessica L. Gordon, Stephen J. LeBlanc, and Todd F. Duffield
This article provides an update on ketosis treatment regimens. The ketosis
treatment literature is reviewed and the findings are summarized. Current
treatment recommendations and areas for future research are provided.
Oral Calcium Supplementation in Peripartum Dairy Cows 447
Garrett R. Oetzel
Hypocalcemia in dairy cattle around parturition can be manifest as clinical
milk fever or subclinical hypocalcemia. Subclinical hypocalcemia has the
greatest economic effect because it affects a much higher proportion of
cows. Oral calcium supplements are used to mitigate the effects of both
forms of hypocalcemia. Oral calcium supplements are appropriate for
cows displaying early clinical signs of hypocalcemia and prophylactically
to lessen the negative impacts of hypocalcemia.
Index 457
x Metabolic Diseases of Dairy Cattle
VETERINARY CLINICS OF
NORTH AMERICA:
FOOD ANIMAL PRACTICE
FORTHCOMING ISSUES RECENT ISSUES
November 2013 March 2013
Heifer Development in Beef Cattle Pain Management
David J. Patterson, PhD, and Johann (Hans) Coetzee, BVSc,
Michael Smith, PhD, Editors Cert CHP, PhD, Editor
March 2014 November 2012
Bovine Orthopedics Diagnostic Pathology
David E. Anderson, DVM, MS, DACVS and Vicky L. Cooper, DVM, MS, PhD, Editor
André Desrochers, DMV, MS, DACVS,
July 2012
DECBHM, Editors
Mastitis in Dairy Cows
Pamela L. Ruegg, DVM, MPVM, Editor
RELATED INTEREST
Veterinary Clinics of North America: Equine Practice
April 2013 (Vol. 29, No. 1)
Topics in Equine Anesthesia
Stuart C. Clark-Price, DVM, MS, Editor
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Metabolic Diseases of Dairy Cattle
Preface
Metabolic Diseases of Dairy
Cattle
Thomas H. Herdt, DVM, MS
Editor
Metabolic disease continues to be a substantial challenge in the dairy industry, not only
in North America but also in all other regions in which modern dairy cattle breeds are
managed and fed for high milk yields. Undoubtedly, some of this continuing challenge
is related to progressive improvement in dairy cow genetics and the ever-increasing
average milk yields of modern dairy cattle. Improvements in production capacity chal-
lenge us to manage and feed cows to allow them to adapt to the tremendous metabolic
demands of high milk production. More than this, however, I believe the continued and
perhaps even enhanced interest in metabolic diseases of dairy cattle comes from our
expanding understanding of the diverse ramifications of the metabolic events of early
lactation. These ramifications go well beyond those associated with traditionally
described metabolic diseases, such as milk fever and ketosis, and include the much
broader realm of nearly all diseases common to early lactation cows. The intertwining
associations among various metabolic stresses and their relationships to other dis-
eases, particularly infectious and inflammatory diseases of early lactation, have now
become a central focus of the interest in metabolic diseases of dairy cattle.
The issue leads off with articles addressing this complex association of metabolism
with other health and nutritional challenges to the dairy cow. The article by Lorraine
Sordillo and William Raphael illustrates the interrelationship of metabolism and inflam-
mation and describes how metabolic events may lead to altered inflammatory re-
sponses and increased susceptibility to infectious diseases. The following article by
Michael Allen and Paola Piantoni addresses new concepts in the potential relationship
between metabolism and appetite regulation, particularly in early lactation cows. Ideas
expressed in this article point to the potential of a “downward spiral” of metabolic
events that may diminish feed intake at the exact time when feed intake should be
increasing. The contributions by Jenne De Koster and Geert Opsomer, and by JR
Roche and coworkers, discuss the long-term implications of body condition and
body condition changes, their effects on insulin resistance, and subsequent effects
Vet Clin Food Anim 29 (2013) xi–xii
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xii Preface
on metabolic health. The articles by Ian Lean and colleagues, in addition to giving
many practical recommendations for dry cow feeding and management, also present
some new ideas and information describing potential mechanisms for an interrelation-
ship and interaction between mineral and energy metabolism. I believe these articles
all broaden the scope of what we’ve traditionally called “metabolic disease.”
Other articles in this issue describe diagnostic tools for the herd-level evaluation of
metabolic status and metabolic disease risk. Some of these are well developed and
others are in development. The article by Paula Ospina and coworkers describes
rigorous new approaches to the herd-level evaluation of serum nonesterified fatty
acid and b-hydroxybutryic acid concentrations. These tests have been in wide appli-
cation for some time and this article offers new insights, particularly into the herd-level
interpretation of these values. The contribution from Giuseppe Bertoni and Erminio
Trevisi points out the potential advantages in creating multivariate testing approaches
to be applied at both the individual animal and the herd level. In this same vein of
describing potentially new testing procedures to aid in the management of metabolic
disease in dairy cows, Jenne Koester and Geert Opsomer describe diagnostic tests
that may become practical in the field for the evaluation of insulin resistance in cows.
Finally, several articles in this issue, including some of those mentioned above,
include sections describing very practical regimens for the management and preven-
tion of metabolic disease in dairy cows. Included among these are those by Jessica
Gordon and colleagues on ketosis therapy and Garrett Oetzel on the prophylactic
use of oral calcium supplements.
I wish to express my admiration for and my appreciation to the contributing au-
thors. They are a distinguished group of international scientists. This issue represents
a worldwide contribution to continuing developments in the investigation, manage-
ment, and prevention of metabolic diseases in dairy cattle.
Thomas H. Herdt, DVM, MS
Department of Large Animal
Clinical Sciences and Diagnostic
Center for Population and Animal Health
College of Veterinary Medicine
Michigan State University
East Lansing, MI 48824, USA
E-mail address:
[email protected] S i g n i f i c a n c e o f M e t a b o l i c S t re s s ,
Lipid Mobilization, and
I n f l a m m a t i o n o n Tra n s i t i o n C o w
D i s o rd e r s
a, b
Lorraine M. Sordillo, MS, PhD *, William Raphael, BVSc, MS
KEYWORDS
Inflammation Lipid mobilization Oxidative stress Transition period Disease
KEY POINTS
The incidence and severity of disease is greatest during the transition period. when immune
functions are impaired.
Intense lipid mobilization is associated with both metabolic and infectious diseases in the
transition cow.
Significant increases in plasma nonesterified fatty acids contribute to oxidative stress and
uncontrolled inflammatory responses.
A dysfunctional inflammatory response is the common link between metabolic and infec-
tious diseases around the time of calving.
Intervention strategies that can reduce lipid mobilization may improve inflammatory
responses and reduce the economic losses associated with health disorders during the
transition period.
Dairy cattle are susceptible to increased incidence of metabolic and infectious dis-
eases during the physiologic transition from late pregnancy to early lactation. Dramatic
changes in both metabolic activity and dysfunctional immune responses are closely
associated with the development of many transition cow disorders.1,2 Although dairy
cows undergo several physiologic changes during the onset of lactation that may
Disclosure: the authors acknowledge research support through grants (2011-67015-30179 and
2012-67011-20019) from the Agriculture and Food Research Initiative Competitive Grants Pro-
grams of the USDA National Institute for Food and Agriculture and by an endowment from the
Matilda R. Wilson Fund (Detroit, MI).
a
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan
State University, 784 Wilson Road, G300 Veterinary Medical Center, East Lansing, MI 48824,
USA; b Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan
State University, 736 Wilson Road, D202 Veterinary Medical Center, East Lansing, MI 48824, USA
* Corresponding author.
E-mail address: [email protected]
Vet Clin Food Anim 29 (2013) 267–278
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268 Sordillo & Raphael
contribute to health problems, the mobilization of excessive body fat reserves and sig-
nificant increases in plasma fatty acid concentration are important risk factors leading
to enhanced disease.3 The direct role that increased lipid mobilization has on liver func-
tion and the pathogenesis of certain metabolic diseases such as fatty liver and ketosis
is well established. However, more recent evidence suggests that increased plasma
fatty acid concentrations may indirectly affect both metabolic and infectious disease
pathogenesis by compromising the function of cells involved in immune responses.
Uncontrolled inflammatory reactions are especially important in the pathogenesis of
several transition cow disorders. A better understanding of the interrelationship be-
tween metabolic stress, lipid mobilization, and immune dysfunction during the transi-
tion period facilitates the design of better control programs to prevent health
disorders during this critical period in the production cycle of dairy cows. This article
addresses the possible linkages between fat mobilization and dysfunctional inflamma-
tory responses that may contribute to increased morbidity and mortality in transition
dairy cows.
PHYSIOLOGIC ADAPTATIONS OF THE TRANSITION COW
The transition period for dairy cows is defined as approximately 3 weeks pre partum
until 3 weeks post partum. Major physiologic, nutritional, metabolic, and immunologic
changes occur within this time frame as the production cycle of the cow shifts from a
gestational nonlactating state to the onset of copious milk synthesis and secretion. For
example, cows must adjust metabolically to the dramatic increase in energy require-
ments that is needed to ensure optimal milk production in the ensuing lactation. Milk
production requires large amounts of carbohydrates for lactose synthesis, and nearly
all the available glucose in the body is diverted to the mammary gland for this purpose.
Dairy cattle experience appetite suppression during the last week of gestation, and it
can take up to a week after calving before dry matter intake (DMI) recovers.4 The
imbalance between energy consumed and the energy needed for production de-
mands is termed negative energy balance (NEB). During times of NEB, sufficient en-
ergy must be mobilized from tissue stores to support energy-dependent needs of
the body, and adipose tissues are a major fuel source for cows during the transition
period. However, a balanced metabolic response during the onset of lactation is
needed to regulate the appropriate amount of lipid mobilization. Initially, a decrease
in blood glucose level occurs in response to both high demands of lactation and dimin-
ished DMI. The reduction in blood glucose results in lower insulin levels, which trigger
the fat mobilization process through lipolysis. During lipolysis, nonesterified fatty acids
(NEFAs) are cleaved from triglyceride molecules within adipocytes through the action
of various hormone-sensitive lipases. NEFA is then transported into the blood by albu-
min, where it can be used as an energy source and also initiate negative feedback
loops to regulate the amount of lipolysis (Fig. 1). The overall cumulative effect should
result in relatively constant blood glucose concentrations needed for milk synthesis
and secretion without excessive NEFA accumulation in the blood.5
Metabolic Stress
Cows successfully adapt to NEB when adipose mobilization is adequately regulated
and the release of NEFA is limited to concentrations that can be fully metabolized
for energy needs. Although lipid mobilization provides the energy needed to promote
milk production, excessive release of lipids from adipose tissues and accumulation of
high concentrations of free fatty acids in the blood are positively correlated to several
metabolic problems in the transition cow.6 The development of ketosis and fatty liver,
Metabolism and Inflammation 269
Fig. 1. Metabolic adaptations during the transition period. There is an increased demand
for available glucose during the transition period to support the onset of lactation. NEB oc-
curs as a result of this increased glucose requirement and reduced DMI. Lower blood glucose
concentrations result in a concomitant decrease in blood insulin concentrations. A decrease
in blood insulin concentrations triggers the release of NEFA from adipose tissues through
the increased activation of lipases. The increase in NEFA is another source of energy that
helps to conserve glucose for milk synthesis. When insulin concentrations increase during
moderate lipid mobilization, the rate of NEFA release from adipose tissue is downregulated
because of the insulin-dependent reduction of lipase activity. However, during intense lipid
mobilization, excessive accumulation of NEFA may interfere with optimal feedback re-
sponses through the increased expression of tumor necrosis factor a (TNF-a). An emerging
hypothesis is that the increased expression of TNF-a may interfere with insulin-dependent
reductions in lipase activity and escalate the accumulation of plasma NEFA. Thus, metabolic
stress results when appropriate metabolic feedback regulation is lost as a consequence of
excessive lipid mobilization, such as in obese humans and transition dairy cows.
for example, is a direct consequence of significant increases in plasma NEFA concen-
trations.5 Recent studies showed that multiparous cows with plasma NEFA concen-
tration higher than 0.57 mEq/L after calving experienced a 600-kg decrease in milk
yield.6 Reduced lactation performance as a consequence of high plasma NEFA con-
centrations can be explained, in part, by the detrimental impact on liver function. When
taken up by hepatocytes, NEFA can be re-esterified to triglycerides or undergo
b-oxidation to generate energy in the mitochondria. However, during intense NEFA
flux, the capacity of hepatocytes to export newly synthesized triglycerides is
exceeded. Excessive triglyceride accumulation in the liver also results in reduced fatty
acid oxidation, which is essential for gluconeogenesis. A reduction in gluconeogenesis
in the liver as a result of triglyceride accumulation limits the available blood glucose
needed for optimal milk production and contributes further to the energy deficits in
the transition cow. The uptake of NEFA in the liver also results in the production of ke-
tone bodies as intermediate products during fatty acid metabolism. Ketones are
released into the blood, where they can be used as energy substrates, especially in
muscle and nerve tissues. Ketosis develops during intense lipid mobilization when
the rate of ketogenesis exceeds ketone body use. The most abundant ketone body,
b-hydroxybutyrate (BHB), is often used to assess the degree of NEB and lipid mobili-
zation in transition dairy cows.
Overconditioned cows with high body condition scores (BCSs) were reported to
have a greater incidence of health problems in the transition period when compared
with leaner cows.7 Cows with a high BCS tend to lose more body weight through lipid
270 Sordillo & Raphael
mobilization, resulting in enhanced increases in NEFA and BHB concentrations during
the onset of lactation. In humans, obesity is associated with insulin resistance, and the
large adipose mass becomes less responsive to the modulating effects of insulin.8
Thus, obesity may exacerbate the severity of metabolic diseases by the formation
of destructive feedback loops that lead to enhanced lipolysis and increased blood
NEFA and BHB concentrations (see Fig. 1). Although the potential of obesity-
induced insulin resistance is not established in cows, there is a model indicating
that this may be the case,9 and excessive body fat is a well-established positive
risk factor for metabolic disorders in cows.3
Inflammatory Response
Intense adipose mobilization may also be a critical factor leading to dysfunction im-
mune responses and infectious diseases during the transition period. Significant in-
creases in lipid mobilization predispose dairy cows to both metabolic (fatty liver,
ketosis) and infectious (mastitis, metritis) diseases.10,11 The transition period is char-
acterized as a time of dramatic changes in the efficiency of the bovine immune system,
which coincides with metabolic stress. Dairy cattle defend themselves from invading
pathogens by a complex network of immune cells and soluble mediators, which are
highly coordinated to provide optimal disease resistance. Inflammation is a critical
component of the initial immune response, which often determines if pathogens are
able to establish disease. The inflammatory process is initiated when localized im-
mune and nonimmune cells within the affected tissues are able to recognize invading
microbes through highly conserved pathogen recognition receptors. The recognition
process activates these resident cell populations and stimulates the release of potent
proinflammatory signaling molecules, including nitric oxide, eicosanoids, and cyto-
kines. These inflammatory mediators can act locally on the vascular endothelium to
increase blood flow and facilitate the migration of leukocytes from the blood to the
site of infection. Newly recruited and preexisting leukocytes, primarily neutrophils
and macrophages, act cooperatively to eliminate microbial pathogens through phago-
cytosis and various intracellular killing mechanisms. Cytokines and eicosanoids can
also elicit systemic inflammatory responses, which include release of acute phase
proteins from the liver, increased body temperature, increased heart rate, and reduced
feed intake. An efficient inflammatory response eliminates the invading pathogen, re-
stores immune homeostasis, and returns tissues back to normal function and
morphology.
Many aspects of the bovine immune system are compromised around the time of
calving, especially with respect to appropriate inflammatory responses.12 There are
several ways that excessive or chronic inflammatory responses can lead to increased
health disorders in the transition cow. During infectious diseases, for example, mac-
rophages and neutrophils are important for the prompt detection and elimination of
invading pathogens. Many studies have documented that the antimicrobial functions
of these leukocyte populations are compromised and certain pathogens are able to
evade local defenses and establish long-term disease. Mastitis caused by either
Staphylococcus aureus or Streptococcus uberis are examples of how widespread im-
mune evasion of mammary gland immune cells can result in chronic inflammation and
extensive tissue damage. Conversely, there are some mastitis-causing pathogens
that can elicit uncontrolled recruitment and activation of inflammatory cells, which
contribute to pathogenesis. Coliform mastitis is more severe during early lactation
when compared with later stages of lactation. Early lactation cows with coliform
mastitis express high milk and serum concentrations of tumor necrosis factor a
(TNF-a), interleukin 1 (IL-1), and IL-6, which are directly related to increased disease
