Influence of calcitonin on eicosanoid serum levels in the treatment of patients with systemic sclerosis

Abstract Background Treatment of scleroderma (systemic sclerosis, SSc) patients (stages I–III) with intravenous (i.v.) calcitonin for 10 days (100 IU/day, Karil ® , Sandoz AG, Germany) 3 times/year leads to subjective and objective improvement of microcirculatory parameters determined by Laser-Doppler fluxmetry and cutaneous pO 2 (pcuO 2 ) measurement. Aim As previously suggested some rheologic effects of calcitonin might be mediated by vasoactive metabolites of the arachidonic acid metabolism. Alterations of eicosanoid plasma levels were determined in 15 SSc patients during i.v. calcitonin therapy. Methods Peripheral blood was obtained on the 1st and 9th days of therapy during a 2 h intravenous calcitonin administration. Samples were taken after 45, 90, 135 and 160 min as well as 1, 5 and 19 days after therapy was stopped. Serum levels of 6-keto-prostaglandin F 1α (6-keto-PGF), a stable end product of prostacyclin synthesis, prostaglandin E 2 (PGE 2 ), leukotriene B 4 (LTB 4 ), and thromboxane B 2 (TXB 2 ) were determined by enzyme- or radio-linked assays. Results In contrast to healthy controls we measured elevated 6-keto-PGF, LTB 4 and PGE 2 serum levels in SSc patients before i.v. treatment, whereas TXB 2 levels showed no significant differences. Calcitonin administration led to an increase of plasma 6-keto-PGF after 45 min falling back to the starting level during further treatment as well as to a longer-lasting increase of PGE 2 on both the 1st and 9th days of therapy. Calcitonin treatment decreased LTB 4 , but did not influence TXB 2 levels significantly during intravenous administration. Conclusion Our data suggest a compensatory mechanism of the damaged vascular system with respect to the PGI 2 (prostacyclin) and PGE 2 formation in SSc patients measured by a constant elevation of these vasodilatory metabolites. LTB 4 may be involved in the microvascular damage in SSc. Calcitonin administration leads to a short-lasting elevation of 6-keto-PGF 1α and an increase of PGE 2 combined with a reduction of LTB 4 resulting in longer-lasting beneficial effects on microcirculatory functions in diseased skin. Since non-steroidal anti-inflammatory agents had no influence on long-term vasoactive effects, improvement of microcirculatory properties by calcitonin may be additionally mediated by smooth muscle relaxation of arterioles.