Cytokines

Mast cells (and basophils) produce many different cytokines that contribute to allergic inflammation (the late-phase reaction). These cytokines include TNF, IL-1, IL-4, IL-5, IL-6, IL-13, CCL3, CCL4, and various colony-stimulating factors such as IL-3 and granulocyte-monocyte colony-stimulating factor (GM-CSF). As mentioned before, mast cell activation induces transcription and synthesis of these cytokines, but preformed TNF may also be stored in granules and rapidly released on FceRI cross-linking. TH2 cells that are recruited into the sites of allergic reactions also produce some of these cytokines. The cytokines that are released from activated mast cells, basophils, and TH2 cells are mainly responsible for the inflammation associated with late-phase reaction. TNF activates endothelial expression of adhesion molecules and together with chemokines accounts for neutrophil and monocyte infiltrates (see Chapter 3). In addition to allergic inflammation, mast cell cytokines also apparently contribute to the innate immune responses to infections. For example, as we will discuss later, mouse models indicate that mast cells are required for effective defense against some bacterial infections, and this effector function is mediated largely by TNF.

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