Intravenous immune
gamma-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-alpha. and
IL-6 receptor (sIL-6R). The levels of
cytokines IL-6,
IL-8, and
TNF-alpha (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-alpha, 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.