Effect of L-arginine and aminoguanidine on the cytokine profile in obstetric antiphospholipid syndrome

Abstract

Antiphospholipid syndrome (APS) is one of the autoimmune causes of miscarriage in pregnancy. We researched the influence of L-arginine (25 mg/kg), the precursor of nitric oxide synthesis, and aminoguanidine, the inhibitor of inducible NO-synthase (10 mg/kg) on the concentration of IL-1β, IL-6, TNF-α, IL-4, IL-10 in serum of BALB/c mice on the 18th day of pregnancy in cases of APS. In the serum of the pregnant mice with APS, an increase in the concentration of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and a decrease in the concentration of anti-inflammatory cytokines (IL-4 and IL-10) was evidenced, relative to those of the pregnant animals without APS. With the use of L-arginine, a decrease in the concentration of IL-1β, IL-6, TNF-α and an increase in the concentration of IL-4 and IL-10 was established, compared with the indicators of the pregnant mice with APS. The introduction of aminoguanidine, the selective inhibitor of iNOS, did not cause any changes in IL-1β, IL-6 and IL-10 compared with the group of animals with APS. However, a decrease in TNF-α concentration and an increase in IL-4 concentration were proved in this series compared with the group of pregnant animals with APS. Combined administration of L-arginine and aminoguanidine caused a decrease in the concentration of IL-1β, IL-6, TNF-α and an increase in the concentration of IL-4 and IL-10, compared with the indicators of the animals with APS. Thus, the combined administration of L-arginine and aminoguanidine to the pregnant mice with APS contributes to the rebalancing of proinflammatory and anti-inflammatory cytokines in the serum more than their individual use.