THE ROLE OF EICOSANOIDS IN THE CHEMOTACTIC RESPONSE TO PASTEURELLA-HAEMOLYTICA INFECTION

The chemotactic role of eicosanoids in the pathogenesis of Pasteurella haemolytica infection was studied, using a tissue chamber infection model and pharmacological inhibitors of eicosanoid synthesis. Tissue chambers were implanted subcutaneously in 12 calves allotted to three treatment groups of equal size. At 45 days after implantation, calves received saline, dexamethasone, or phenylbutazone treatments, and tissue chambers in all animals were then inoculated with P. haemolytica. Chamber fluid samples were collected before inoculation and at 2, 6, 18, 40, and 90 h after inoculation. Bacterial counts, total leukocyte counts, pH and albumin concentrations in chamber fluids were determined using standard bacteriological and clinical pathological methods. Concentrations of eicosanoids and activity of interleukin-1 (IL-1) were measured by radioimmunoassay and a helper T cell bioassay, respectively. Concentrations of leukotriene B-4, (LTB(4)), thromboxane B-2 (TXB(2)), 6-keto-prostaglandin F-1 alpha. (PGF(1 alpha)) and prostaglandin E(2) (PGE(2)) increased markedly after inoculation. An inhibitory effect of dexamethasone on both LTB(4) production and neutrophil influx, together with the temporal relationship between these two events, suggested that LTB(4) served as a chemo-attractant. Activity-time profiles for IL-1 in chamber fluids were similar to those of the eicosanoids. Phenylbutazone and dexamethasone reduced the severity of the inflammatory responses as measured by lower concentrations of albumin and higher pH in treated versus control chamber fluids. The results of this study suggest that eicosanoid inflammatory mediators pray an important chemotactic role in the pathogenesis of P. haemolytica infection.