Cytokines and neopterin in antiphospholipid syndrome

Abstract

Objective. To study clinical significance of proinflammatory cytokines (tumor necrosis factor α – TNFα, interleukine 6 – IL6, IL18), soluble receptors of TNFα (sTNF-R), anti- inflammatory cytokines (IL10) and integral marker of cytokine-dependent cell immune response activation neopterin in antiphospholipid syndrome (APS).Material and methods. Serum concentration of cytokines and neopterin was evaluated by immunoenzyme assay with commercial kits “BioSource International, Inc.” (USA), “Bender MedSystems” (Austria) and “IBL” (Germany) in 39 pts with primary APS (PAPS), 53 pts with secondary APS (SAPS) associated with systemic lupus erythematosus (SLE), 164 pts with SLE and 54 healthy donors.Results. Level of Th1 cytokines (TNFα, IL18), sTNF-R and neopterin in PAPS, SAPS and SLE as well as Th2 cytokines (IL6, IL10) in SAPS and SLE were significantly higher than in donors (p<0,05). TNFα elevation in PAPS was associated with damage of cardiac valves (p<0,05) and CNS (p<0,01), IL18 elevation – with chronic leg ulcers (p<0,001). Most prominent sTNFα-R elevation in SAPS was revealed in pts with thrombocytopenia (p<0,05). Neopterin hyperproduction in APS was associated with cardiac valve damage16 (p<0,001). IL10 level elevation in APS correlated with decreased thrombosis history (r=- 0,4; p<0,02), in SLE with APS – with decrease of damage score SLICC (r=-0,7; p<0,001) what proves protective significance of IL10 in relation to thrombosis development and disease progression. Increased concentration of IL 18 was associated with atherogenic disturbances presented as hypertrigliceridemia (r=0,6; p<0,01) and decrease of HDLP cholesterol (r—0,4; p<0,01). Positive correlation between TNFα, IL6 and neopterin level, IgM anticardiolipine antibodies and IgG/IgM antiprothrombin antibodies (p<0,05) was revealed. Cytokine, sTNFα-R and neopterin level elevation in SLE with APS was associated with increase of SLEDAI and ECLAM activity indices (p<0,05). Conclusion. Cytokine and neopterin hyperproduction reflecting cell immunity activation and inflammation is an important factor of APS pathogenesis.