Natural and therapeutically-induced antibodies to cytokines.

Serum samples obtained from non-immunocompromised patients treated therapeutically with recombinant cytokines (e.g. Il-1alpha; Il-1beta; Il-2 to Il-18; IFNalpha; GM-CSF; G-CSF; etc.) often reveal the presence of high affinity anti-cytokine antibodies. Antibody Fab binding in a saturable manner by ELISA and RIA or western immunoblotting prove their specificity. Antibody level often increases in these patients with repeated cytokine administration, suggesting boosts of antigen stimulation. However, the appearance in circulation of auto-antibodies to exogenous cytokine is not always associated with a decreased clinical response to therapy. The demonstration that non-neutralizing auto-antibodies to several natural cytokines can be found even in sera of normal healthy individuals never treated before with cytokines and particularly during the last trimester of pregnancy and in cord-blood, suggests that these naturally- occurring and therapeutically-induced auto-antibodies may exert different functions, not only as inhibitors or antagonists but also as beneficial physiological cytokine carriers or regulators of their activity.