Relationship of inflammatory cytokines, growth hormone, and insulin-like growth factor-I to reduced performance during infectious disease.

Production of inflammatory cytokines and concentrations of growth hormone and insulin-like growth factor-I (IGF-I) were studied during experimental Escherichia coli mastitis to determine their potential involvement in reduced animal performance during infectious disease. During the first 10 to 14 hr after intramammary infusion of E. coli, bacteria multiplied to maximum levels of 10(4)-10(9) cfu/ml of milk with no clinical signs of mastitis. A rapid and intense inflammatory response, characterized by udder swelling, increased bovine serum albumin (BSA) and somatic cell count (SCC) in milk of infected glands, and elevated rectal temperature and serum cortisol concentration, began at approximately 12 hr after challenge. Lactational performance was reduced greatly at 24 hr, and the maximal decrease averaged 76% and 63% among infected and uninfected glands, respectively, of challenged cows; three cows became temporarily agalactic in all glands. By 6 days, all cows had nearly or completely eliminated the E. coli, and milk production had partially recovered. Milk composition showed an initial decrease in fat percentage followed by an increase thereafter. Protein percentage was increased and lactose content was reduced during most of the mastitic episode. High concentrations of tumor necrosis factor (TNF) and interleukin-1 (IL-1) were detected in milk of infected glands, and their appearance preceded or coincided with development of the mammary inflammation, systemic reaction, and hypogalactia. Serum growth hormone concentration was higher among challenged cows, whereas serum IGF-I concentrations changed little during the mastitic episode. Concentrations of IGF-I in milk whey increased from 5.0 to 12.2 ng/ml among infected glands and from 4.4 to 8.5 ng/ml among contralateral, uninfected glands; IGF binding proteins also increased in the milk of infected glands. These data demonstrate that (i) reduced lactational performance is not caused by reduced concentrations of growth hormone or IGF-I and (ii) inflammatory cytokines are produced at a time consistent with a possible role in the inhibition of milk synthesis.