Balance of Th1/Th2 cytokines in thyroid autoantibody synthesis in vitro

Thyroid-infiltrating lymphocytes spontaneously synthesize IgG class thyroid autoantibodies while blood lymphocytes require activation to produce the s ame autoantibodies, Surprisingly, the stimulus commonly used to induce auto antibodies by blood lymphocytes, Pokeweed mitogen (PWM), inhibits autoantib ody synthesis by thyroid lymphocytes, To address this dichotomy, we investi gated the Th1:Th2 cytokine balance in relation to thyroid peroxidase (TPO) autoantibody production in cultures of thyroid, lymph node and blood lympho cytes, The characteristic PWM effect on TPO autoantibody production by thyr oid and blood lymphocytes (10 day cultures) was confirmed. Cytokine measure ments in these cultures revealed that PWM increased IFN-gamma production by thyroid, lymph node and blood lymphocytes, However, PWM enhanced IL-4 leve ls in lymphocytes from blood and lymph node but not in thyroid lymphocytes, Moreover, the IL-4:IFN-gamma ratios in short- and longterm cultures were h igher for PBMC and lymph node lymphocytes than for thyroid lymphocytes, In summary, PWM shifts the cytokine balance towards Th2 for blood lymphocyt es and towards Th1 for thyroid lymphocytes, The shift towards Th1 in the ta rget organ is associated with reduced autoantibody synthesis, Our observati ons suggest that "immune deviation" towards Th2 as a form of therapy in Gra ves' disease could project the patient from the frying pan into the fire,