Efficacy of Tumor Necrosis Factor-α and Antibiotics in Therapy of Experimental Murine Staphylococcal Mastitis

Abstract

The mouse model was used to determine the efficacy of the cytokine, tumor necrosis factor-α, and antibiotic in treatment of experimentally induced staphylococcal mastitis. Recombinant human tumor necrosis factor-α alone administered to the mammary glands of lactating mice recruited significantly more polymorphonuclear neutrophils into the gland by 4h posttreatment than did the untreated control. One hundred times less recombinant mouse tumor necrosis factor-α than human tumor necrosis factor-α was required to enhance the killing of Staphylococcus aureus within the gland. Human tumor necrosis factor-α effectively enhanced the killing of the bacteria when it was administered 4 to 0h prior to infection, but not 4h after infection. When mice were first pretreated with tumor necrosis factor-α, infected, and then treated with antibiotics (ciprofloxacin and pirlimycin, but not cloxacillin), the combination of antibiotic and cytokine significantly reduced the number of bacteria within the gland compared with that for mice treated with antibiotic alone, cytokine alone, or placebo. Recombinant tumor necrosis factor-α may be an effective adjunct to antimicrobial therapy in treatment of staphylococcal mastitis in the bovine.