Excretion of metabolites of prostacyclin and thromboxane by rats with nephrotoxic nephritis: effects of interleukin‐1

1 To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti‐glomerular‐basement‐membrane antibodies (a‐GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a‐GBM. 2 Administration of a‐GBM (9.5 mg) caused albuminuria, decreased creatinine clearance, increased numbers of intra‐glomerular neutrophils and increased excretion of TXB2, 2,3‐dinor‐TXB2 (products of TXA2) and 6‐oxo‐PGF1α and 2,3‐dinor‐6‐oxo‐PGF1α (products of PGI2) at 24 h. 3 Interleukin‐1 (IL‐1β; 5 μg) alone caused an increase in PGI2 metabolite excretion but had no effect on TXA2 metabolites. It had no effect on creatinine clearance but increased numbers of glomerular neutrophils by approximately 4–5 fold compared to a‐GBM. 4 Pretreatment of rats with IL‐1β before a‐GBM synergistically increased albumin excretion but only additively increased eicosanoid excretion. Numbers of intra‐glomerular neutrophils and creatinine clearance were unchanged compared to IL‐1β alone. 5 The cyclo‐oxygenase inhibitor, ibuprofen (10 mg kg−1 i.p., twice daily for 4 days) inhibited both serum TXB2 production and urinary prostaglandin excretion. It also caused an almost complete attenuation of albumin excretion. Creatinine clearance and glomerular neutrophils remained unchanged after a‐GBM/IL‐1β. 6 We conclude that the 50% inhibition of thromboxane production induced by ibuprofen does not modify the fall in creatinine clearance of accumulation of neutrophils in the glomerulus caused by the a‐GBM. This degree of inhibition of eicosanoid production was associated with a striking decrease in proteinuria, but this may reflect a haemodynamic rather than a disease modifying action.