The objective of this study was to review the possible relationships betwee
n hyperketonemia and the function of phagocytes with respect to the bovine
udder defense mechanism. We hypothesize that an increased incidence of clin
ical mastitis in high-producing cows is caused by the impairment of the udd
er defense mechanism during hyperketonemia. First, we review the acute phas
e of udder defense mechanisms after intramammary infection. The physiologic
al changes of cows in negative energy balance are subsequently discussed. F
inally, possible relationships between udder defense and physiological chan
ges during negative energy balance, especially hyperketonemia, are reviewed
. The three stages of an acute phase of udder defense are: (1) immediately
eliminating invading pathogens by phagocytes, (2) releasing inflammatory su
bstances, especially chemoattractants, and (3) migration of polymorphonucle
ar leukocytes into the infected udder. Leukocytes from hyperketonemia subje
cts show a lower capacity of the phagocytic defense mechanism. In addition,
the phagocytic and bactericidal capacities of neutrophils are reduced when
these cells are acting in the presence of high concentrations of ketone bo
dies. Lower amounts of cytokine production after bacterial infection are ob
served in ketotic subjects. The chemotactic capacity of blood leukocytes is
impaired in leukocytes obtained from ketotic cows. Lower numbers of blood
leukocytes are observed in ketotic cows. In conclusion, the impairment of t
he udder defense mechanism in negative energy balance cows seems related to
hyperketonemia.