Effect of 5-hydroxypyrimidine derivatives and reference drug Aerius on systemic anaphylaxis, concentration of immunoglobulin E and cytokines tested in Balb/c mice

Abstract

Imbalance of Th1/Th2 lymphocytes and cytokines is responsible for increasing rate of pathology, such as allergy, autoimmune processes and cancer. Pyrimidines have a wide spectrum of pharmacological activity, for example antiallergic properties. The aim of this study is to investigate effects of 5-hydroxypyrimidine derivatives on systemic anaphylaxis, concentrations of immunoglobulin E (IgE) and cytokines in comparison with Aerius in experiments on ovalbumin-induced systemic anaphylaxis model. Effects of 7-day course of intraperitoneal (i/p) administration of SNK-411, SNK-578 at the doses of 25 mg/kg and 50 mg/kg, Aerius (i/p, 1.3 mg/kg) were studied in 140 male Balb/c ovalbumin-sensitized mice. 120 mice were immunized by two injections (two-week interval) of ovalbumin (100 mg per mouse) mixed with aluminum hydroxide (5 mg per mouse). 20 mice were used as intact control. Administration of SNK-411, SNK-578, or Aerius began after second immunization and lasted for 7 days. Within one hour after last injection of the compounds, 70 mice received injection of ovalbumin (100 mg dissolved in 0.1 mL saline) in retroorbital sinus. 70 mice from control and experimental groups were euthanized by decapitation. IgE, Interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, IL-11, IL-17A, IL-17F, Interferon gamma (IFNγ), IL-13 concentrations were measured in blood sera. Administration of SNK-411, SNK-578 at the dose of 50 mg/kg decreased systemic anaphylaxis, lowered IgE concentration by 1.5-1.6 times compared to ovalbumin control group whereas Aerius did not reduce concentration of IgE. Administration of SNK-411, SNK-578 at 25 mg/kg, and 50 mg/kg, and Aerius decreased concentration of Th-2 cytokines (IL-4, IL-5, IL-13) compared to ovalbumin-treated control group. SNK-411, SNK-578 at the doses of 25 mg/kg and 50 mg/kg increased level of IL-2. SNK-578 at 50 mg/kg increased concentration of IFNγ up to intact control level and decreased concentration of IL-6. 7-day administration of 5-hydroxypyrimidine derivatives at the dose of 50 mg/kg decreased severity of systemic anaphylaxis. SNK-411, SNK-578, Aerius lowered levels of proallergic cytokines in serum of sensitized mice. In contrast to Aerius, the 5-hydroxypyrimidine derivatives decreased serum IgE concentrations.

Keywords

• anaphylaxis
• 5-hydroxypimidines
• desloratadine
• immunoglobulin e
• allergy
• cytokines