Reduced production of IL-12 and IL-12-dependent IFN-gamma release in patients with allergic asthma.

TC Van der Pouw Kraan, LC Boeije… - … (Baltimore, Md.: 1950 …, 1997 - journals.aai.org
TC Van der Pouw Kraan, LC Boeije, ER de Groot, SO Stapel, A Snijders, ML Kapsenberg…
Journal of immunology (Baltimore, Md.: 1950), 1997journals.aai.org
In atopic patients, allergen-specific T cells have acquired the Th2 phenotype, which is
considered to be responsible for the class switch to IgE Ab formation. Because IL-12 is a key
cytokine for the induction of Th1 responses, a reduced capacity to produce this cytokine
could lead to aberrant Th2 development. Therefore, we examined the production of IL-12 in
whole blood cultures from patients with allergic asthma (n= 15) in comparison with
nonatopic control subjects (n= 15) to different stimuli. After stimulation with Staphylococcus …
Abstract
In atopic patients, allergen-specific T cells have acquired the Th2 phenotype, which is considered to be responsible for the class switch to IgE Ab formation. Because IL-12 is a key cytokine for the induction of Th1 responses, a reduced capacity to produce this cytokine could lead to aberrant Th2 development. Therefore, we examined the production of IL-12 in whole blood cultures from patients with allergic asthma (n = 15) in comparison with nonatopic control subjects (n = 15) to different stimuli. After stimulation with Staphylococcus aureus Cowan I strain (SAC) we observed a 2.6-fold reduction of IL-12 p70 production in the patient group (p < 0.005). This was not due to a general failure of monocytes from these patients to produce cytokines, because the production of IL-6 was normal. SAC also induced the production of IFN-gamma, which was blocked by neutralization of IL-12. In line with the reduced levels of IL-12 secretion, the patient group showed a 3-fold reduction of IL-12-dependent IFN-gamma production (p < 0.005). The amounts of IL-12 and IFN-gamma were positively correlated in both the patient (R = 0.51 at 0.05% SAC and R = 0.64 at 0.01% SAC) and the control groups (R = 0.64 at 0.05% SAC and R = 0.70 at 0.01% SAC). The IFN-gamma:IL-12 ratio was not different between patients and control subjects, indicating a normal response to IL-12. Diminished production of IL-12 and IFN-gamma could not be explained by an increased production of IL-10, because in SAC-stimulated cultures IL-10 was hardly induced in both groups. Furthermore, after stimulation with Escherichia coli, the production of IL-10 was similar in patients and control subjects.
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