Monesha Gupta

Cytokine Modulation with Immune γ-Globulin in Peripheral Blood of Normal Children and Its Implications in Kawasaki Disease Treatment

Intravenous immune γ-globulin (IVIG) is used successfully in the treatment of Kawasaki disease, with dose-dependent rapid resolution of symptoms such as fever and irritability and a decrease in ESR, WBCs, and platelets. The mode of action of IVIG in reducing this inflammatory response is not clearly understood. Recently anticytokine antibodies in IVIG have been demonstrated. Serum levels of proinflammatory cytokines have been shown to be elevated in patients with Kawasaki disease. The cytokine interleukin-6 (IL-6) is involved in the de novo production of acute-phase proteins by hepatocytes and cause thrombocytosis and fever in response to tissue injury. Patients receiving parenteral recombinant human IL-6 have dose-dependently experienced fever, malaise, chills, and acute-phase reaction. With high IL-6 concentrations, central nervous system toxicity has also been reported and IL-6 has been thought to mediate endothelial damage. We evaluated the response of stimulated blood cells of 12 normal children to IVIG in the release of the cytokines IL-6, IL-8, TNF-α, and IL-6 receptor (sIL-6R). The levels of cytokines IL-6, IL-8, and TNF-α (but not sIL-6R) in peripheral blood induced by stimulation with LPS were markedly reduced (P < 0.008) within 3 hr when incubated with IVIG compared to without IVIG. Thus we demonstrated that cells of normal children respond to IVIG in vitro by reducing cytokines such as IL-8, TNF-α, and IL-6 without affecting the level of receptor sIL-6R during an acute inflammatory response. We also found significantly higher IL-6 levels in children with Kawasaki disease compared to children with blood culture-negative febrile illnesses. In five children with Kawasaki disease we measured serum IL-6 before and after IVIG and assessed the clinical response to IVIG therapy. Therapy with IVIG was followed by a rapid resolution of symptoms in Kawasaki disease, with a significant decrease in serum IL-6. The attenuation of proinflammatory cytokine responses, especially IL-6, following infusions of IVIG may play an integral role in the rapid resolution of symptoms and decrease in the acute-phase proteins in children with Kawasaki disease. Cells of normal children were found to respond to the IVIG in a manner similar to that of the Kawasaki children.

Elevated IgA and IgM Anticardiolipin Antibodies in Acute Kawasaki Disease

There is marked activation of the endothelium and immune system in Kawasaki disease. Anticardiolipin antibodies (aCL) can cause activation of the endothelium. We measured aCL levels in acute Kawasaki disease patients and compared them to other febrile patients to see whether their aCL responses were different. Twenty-one patients with acute Kawasaki disease and 16 patients with an acute febrile illness were recruited. The aCL levels were measured in the sera of febrile patients and in Kawasaki disease patients prior to immunoglobulin therapy. There was no significant difference between the IgG aCL levels (p = 0.87) between the Kawasaki disease and febrile patients. However, the IgM (p = 0.01) and IgA (p = 0.03) aCL were significantly higher in patients with acute Kawasaki disease than in febrile children. Elevation of IgA aCL has been reported in association with other vasculitides and IgA-secreting plasma cells have been demonstrated in the vascular tissue in Kawasaki disease.

Relation of early pleural effusion after pediatric open heart surgery to cardiopulmonary bypass time and systemic inflammation as measured by serum interleukin-6.

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Troponin I as a Marker for Myocardial Injury and Ischemia during Pediatric Cardiopulmonary Bypass Surgery

Troponin I as a Marker for Myocardial Injury and Ischemia during Pediatric Cardiopulmonary Bypass Surgery