Cytokine enhancement of anaphylaxis.
Two distinct pathways of anaphylaxis in the mouse have similar clinical features: the classical pathway in which antigen cross-linking of IgE bound to FcepsilonRI on mast cells induces histamine release, and a second pathway, in which cross-linking of macrophage FcgammaRIII by antigen-IgG complexes induces release of platelet activating factor. IgG antibodies are a double-edged sword, blocking the first pathway but mediating the second. Both anaphylaxis pathways are considerably enhanced by interleukin (IL)4 or IL13 through a Stat6-dependent, gammac-independent mechanism. Enhancement is rapid, sensitive, and observed during infection with intestinal nematode parasites, where it probably contributes to parasite expulsion. Enhancement involves increased sensitivity to mediators (platelet activating factor, histamine, serotonin, and cysteinyl leukotrienes), rather than increased mediator production, and is mediated by a synergistic increase in vascular permeability by cytokine plus mediator. Basophil production of IL4 and IL13, which is more sensitive to FcepsilonRI cross-linking than mast cell release of mediators, may sensitize target cells to mediators prior to their release. Inhibitors of IL4 and IL13 may ameliorate allergy by rapidly blocking the sensitizing effects of these cytokines on the effector phase of the allergic response, as well as by more slowly blocking the induction phase of this response.
Strait
Richard
R
Division of Emergency Medicine, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Morrist
Suzanne C
SC
Finkelman
Fred D
FD
D000707:Anaphylaxis / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001491:Basophils / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000276:immunology / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism
D016207:Cytokines; D007074:Immunoglobulin G; D018793:Interleukin-13; D010455:Peptides; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D015847:Interleukin-4; D007073:Immunoglobulin E