Effects of cyclooxygenase inhibition on the response to group B streptococcal toxin in sheep

The effects of cyclooxygenase inhibition on the reaction to a toxin isolated from group B beta-hemolytic streptococci, type III, were studied in seven sheep instrumented for chronic measurement of pulmonary lymph flow, pulmonary artery and left atrial pressures. Each sheep was infused with toxin alone on one day and with indomethacin plus toxin on a different day in random order. The toxin alone caused a two-phased reaction. After the infusion of toxin, alone, in the initial phase, pulmonary artery pressure increased from 16.5 +/- 1.2 mmHg to 47.1 +/- 4.8 mmHg and the rectal temperature rose from 39.7 +/- 0.13 degree C to 40.9 +/- 0.16 degree C. During the second phase, the granulocyte count decreased to less than 10% of baseline values and the lymph protein clearance increased from 4.8 +/- 1.2 ml/h to 10.02 +/- 1.4 ml/h, suggesting increased pulmonary vascular permeability. Indomethacin pretreatment prevented the initial phase of pulmonary hypertension, the increases in thromboxane and prostacyclin metabolites in lung lymph, and the febrile response to toxin infusion but did not modify the granulocytopenia or the increased pulmonary vascular permeability. It appears that the hemodynamic changes are independent from the pulmonary vascular changes, and that prostaglandin endoperoxides or their metabolites are necessary for the fever and the acute pulmonary hypertension.