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 ph enotype, which is considered to be responsible for the class switch to IgE Ab formation, Because IL-12 is a key cytokine for the induction o f Th1 responses, a reduced capacity to produce this cytokine could lea d to aberrant Th2 development. Therefore, we examined the production o f IL-12 in whole blood cultures from patients with allergic asthma (n = 15) in comparison with nonatopic control subjects (n = 15) to differ ent stimuli, After stimulation with Staphylococcus aureus Cowan I stra in (SAC) we observed a 2.6-fold reduction of IL-12 p70 production in t he patient group (p < 0.005). This was not due to a general failure of monocytes from these patients to produce cytokines, because the produ ction 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 reduc ed levels of IL-12 secretion, the patient group showed a 3-fold reduct ion of IL-12-dependent IFN-gamma production (p < 0.005). The amounts o f 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 group s (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, indi cating 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 gr oups, Furthermore, after stimulation with Escherichia coli, the produc tion of IL-10 was similar in patients and control subjects.