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Inducing and enhancing effects of IL-3, -5, and -6 and GM-CSF on histamine release from human basophils
A Miadonna1, M G Roncarolo, M Lorini
1Department of Internal Medicine, Infectious Diseases, and Immunopathology, University of Milan, Ospedale Maggiore Policlinico, Italy.
Abstract:
The effects of interleukin (IL)-2, -3, -4, -5, -6, and -7 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on histamine release from human basophils were evaluated. IL-3 was the only cytokine with histamine-releasing activity. This activity was observed predominantly on basophils from allergic patients (mean release +/- SEM, 33.9 +/- 9.5%; n = 12), whereas basophils from normal subjects responded less frequently to stimulation with IL-3 (mean release +/- SEM, 2.8 +/- 1.0%; n = 22). The effect of IL-3 was time and temperature dependent, since release was optimal after incubation for 120 min at 37 degrees C. When cell-bound IgE were eluted at acid pH, basophils became unresponsive to IL-3; however, IL-3-induced histamine release correlated with anti-IgE-induced histamine release in allergics, but not in normals. IL-3, IL-5, IL-6, and GM-CSF enhanced significantly anti-IgE- and FMLP-induced histamine release. In contrast, IL-2, IL-4, and IL-7 were devoid of any significant histamine-releasing or -potentiating activity. These results indicate that IL-3 can induce and IL-3, -5, and -6 and GM-CSF can enhance histamine release from human basophils, suggesting a possible role of these cytokines in the expression of allergic reactions.
Insights
Interleukin-3 (IL-3) is the only tested cytokine that directly triggers histamine release from human basophils, particularly in allergic individuals. Other cytokines like IL-5, IL-6, and GM-CSF can enhance this release.
Area of Science:
- Immunology
- Cell Biology
- Allergy Research
Background:
- Human basophils play a key role in allergic reactions through histamine release.
- Cytokines are signaling molecules that modulate immune responses, but their specific roles in basophil activation are not fully understood.
Purpose of the Study:
- To investigate the effects of various interleukins (IL-2, -3, -4, -5, -6, -7) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on histamine release from human basophils.
- To determine which cytokines can directly induce histamine release and which can potentiate allergen- or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced release.
Main Methods:
- Human basophils were isolated and incubated with different cytokines.
- Histamine release was measured after stimulation with individual cytokines or in combination with anti-IgE or fMLP.
- The role of IgE in IL-3-induced histamine release was assessed by eluting cell-bound IgE.
Main Results:
- Interleukin-3 (IL-3) was the sole cytokine demonstrating direct histamine-releasing activity, predominantly from basophils of allergic patients.
- IL-3-induced histamine release was dependent on time, temperature, and the presence of IgE.
- IL-3, IL-5, IL-6, and GM-CSF significantly enhanced histamine release induced by anti-IgE and fMLP.
- IL-2, IL-4, and IL-7 showed no significant histamine-releasing or potentiating activity.
Conclusions:
- IL-3 can directly induce histamine release from human basophils, especially in allergic individuals.
- IL-3, IL-5, IL-6, and GM-CSF can enhance histamine release, suggesting their involvement in allergic reactions.
- These findings highlight the potential role of specific cytokines in the pathophysiology of allergic responses.