Modulation of endotoxin-induced inflammation in the bovine teat using antagonists/inhibitors to leukotrienes, platelet activating factor and interleukin 1 beta.
A leukotriene biosynthesis inhibitor (MK886), a platelet-activating factor (PAF)-receptor antagonist (WEB 2086), a recombinant human interleukin-1 receptor antagonist (IL-1ra) and a polyclonal antibody to recombinant bovine IL-1 beta (anti-rBoIL-1 beta) was used to investigate the involvement of leukotrienes, PAF and IL-1 beta during endotoxin-induced inflammation in the bovine teat cistern. Endotoxin alone was infused into one teat cistern and endotoxin in combination with an inhibitor/antagonist was infused into another teat cistern of the same animal. Teat cistern samples were taken before infusion and at 3.5 and 7 h after infusion, and the numbers of neutrophils were counted. Saline infusion was used as control. The inhibitors/antagonists were also tested in combination with leukotriene B4 (LTB4), PAF and rBoIL-1 beta, respectively. MK886 or WEB 2086 significantly reduced the accumulation of neutrophils mainly between 3.5 and 7 h after infusion, indicating roles for leukotrienes, probably LTB4, and PAF in neutrophil accumulation during endotoxin-induced inflammation. As WEB 2086 also reduced cell accumulation between 0 and 3.5 h, PAF was implicated also in the early influx of neutrophils. WEB 2086 almost completely inhibited PAF-induced cell accumulation between 0 and 3.5 h. LTB4 did not induce significant cell accumulation in the teat cistern. IL-1ra did not affect endotoxin-induced neutrophil accumulation whereas anti-rBoIL-1 beta reduced total cell accumulation and, to some degree, accumulation between 0 and 3.5 h after infusion. Infusion of IL-1ra significantly inhibited cell accumulation induced by rBoIL-1 beta. Anti-rBoIL-1 beta also significantly reduced neutrophil accumulation induced by rBoIL-1 beta, but to a lesser degree. The results suggest roles for leukotrienes, most likely LTB4, and PAF, and to a lesser extent IL-1 beta, during endotoxin-induced neutrophil migration into the bovine teat cistern. The potential of the inhibitors/antagonists as therapeutic agents for bovine mastitis should be investigated.
Waller
K P
KP
Swedish University of Agricultural Sciences, Faculty of Veterinary Medicine, Department of Obstetrics and Gynaecology, Uppsala. karin.persson@og.slu.se
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000276:immunology; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors*; D002417:Cattle; D004731:Endotoxins; D005260:Female; D005343:Fibrinolytic Agents / Q000276:immunology; D006801:Humans; D007211:Indoles / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors / Q000276:immunology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000276:immunology*; D008414:Mastitis, Bovine / Q000209:etiology / Q000276:immunology*; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012795:Sialoglycoproteins / Q000276:immunology; D014230:Triazoles / Q000276:immunology; D002722:Chlorobenzenes
D000276:Adjuvants, Immunologic; D001381:Azepines; D001779:Blood Coagulation Factors; D004731:Endotoxins; D005343:Fibrinolytic Agents; D007211:Indoles; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014230:Triazoles; C507763:IL1RN protein, human; C060893:MK-886; D002722:Chlorobenzenes; C052518:WEB 2086