Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome.
Kawasaki syndrome (KS) is an acute febrile illness of early childhood characterized by diffuse vasculitis and marked immune activation. The present study was undertaken to determine whether the acute phase of KS is associated with circulating cytotoxic antibodies directed to target antigens induced on vascular endothelium by the monokines, IL-1, or tumor necrosis factor (TNF). Sera from 20 patients with acute KS, 11 patients in the convalescent phase of KS, and 17 age-matched controls were assessed for complement-dependent cytotoxic activity against 111In-labeled human endothelial cells (HEC), dermal fibroblasts, and vascular smooth muscle cells. Sera from patients with acute KS but not the other subject groups caused significant (p less than 0.01) complement-mediated killing of IL-1- or TNF-stimulated HEC. None of the sera tested had cytotoxicity against control HEC cultures or the other target cell types, with or without IL-1 or TNF pretreatment. Expression of the IL-1- or TNF-inducible target antigens on endothelial cells was rapid and transient, peaking at 4 h and disappearing after 24 h despite continued incubation with monokine. In contrast, we have previously shown that IFN-gamma requires 72 h to render HEC susceptible to lysis with acute KS sera. Serum adsorption studies demonstrated that IL-1- and TNF-inducible endothelial target antigens are distinct from IFN-gamma-inducible antigens. These observations suggest that mediator secretion by activated monocyte/macrophages could be a predisposing factor to the development of vascular injury in acute KS. Although our present observations have been restricted to KS, the development of cytotoxic antibodies directed to monokine-inducible endothelial cell antigens may also be found in other vasculitides accompanied by immune activation.
D000906:Antibodies / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002675:Child, Preschool; D004727:Endothelium / Q000187:drug effects; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha; D014680:Veins / Q000166:cytology / Q000187:drug effects*
D000906:Antibodies; D000954:Antigens, Surface; D006023:Glycoproteins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha