ASPIRIN-INTERLEUKIN-3 INTERRELATIONSHIPS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

PROBLEM: Previously we reported on the generation of experimental anti -phospholipid syndrome (APS) in mice. These models were employed to ev aluate the efficacy of various novel therapeutic modalities including interleukin-3 (IL-3) and low dose aspirin. The efficacy of the latter was found to be interrelated. Low dose aspirin is capable of inhibitin g the activity of the enzyme cyclooxygenase which is responsible for t he metabolism of arachidonic acid towards the production of prostaglan dins. This shifts the metabolism of arachidonic acid to the other path way and leads to an overproduction of leukotrienes. The leukotrienes a ct as stimulators of IL-3 production, a positive cytokine in pregnancy which enhances placental and fetal development. In the current study we evaluated the IL-3 levels in pregnant women with APS and expanded o ur knowledge on the interrelationships between aspirin, arachidonic ac id metabolites and IL-3 in the human system. METHODS: IL-3 levels were recorded in the serum of pregnant women with APS and compared to a co ntrol pregnant group. In addition peripheral blood mononuclear cells f rom healthy subjects were incubated with different concentrations of a spirin or with arachidonic acid metabolites (Leukotriene B4, C4 or PGE (2)), and IL-3 production in the culture fluids was evaluated. RESULTS : Serum level of IL-3 in pregnant patients with primary APS, APS secon dary to SLE and SLE was lower in comparison to the control group. The in vitro studies revealed that only low dose aspirin (10 mg/mu l) stim ulated IL-3 production while higher doses of the drug failed to induce the cytokine generation. Leukotriene B4 and C4 were stimulatory where as PGE(2) acted as inhibitor of IL-3 production. CONCLUSIONS: The seru m level of IL-3 is decreased to pregnant women with primary or seconda ry APS. Low dose aspirin is capable of stimulating IL-3 production in vitro most probably through an elevation of leukotriene production, wh ich may explain its beneficial activity in preventing the manifestatio ns of APS.