Reduced production of IL-12 and IL-12-dependent IFN-gamma release in patients with allergic asthma.
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.
van der Pouw Kraan
T C
TC
Department of Auto-Immune Diseases, the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Boeije
L C
LC
de Groot
E R
ER
Stapel
S O
SO
Snijders
A
A
Kapsenberg
M L
ML
van der Zee
J S
JS
Aarden
L A
LA
D000328:Adult; D001249:Asthma / Q000097:blood / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018418:Th2 Cells / Q000276:immunology*
D018664:Interleukin-12; D007371:Interferon-gamma