Histamine-releasing factors and inhibitors: historical perspectives and possible implications in human illness

The initiation of allergic reactions with the bridging of surface-bound IgE antibodies on mast cells and basophils by allergens is well recognized. However, it is clear that other factors most likely play a role in regulating these cells. A number of cytokines have been identified that modulate the secretory response of mast cells and basophils. Among the well-characterized cytokines, interleukin-3 and connective tissue-activating peptide III (or its degradation product, neutrophil-activating peptide 2) can increase the secretory response, whereas interleukin-8 specifically inhibits the response to cytokines. Additional factors are currently under investigation. Preliminary studies suggest an important role for these histamine-releasing factors in atopic disorders, as well as in other conditions in which an IgE-dependent mechanism is not demonstrable. Furthermore, these cytokines may modulate the response of basophils and mast cells in physiologic conditions, such as tissue repair and host defense.