ANALYSIS OF GRANULOMA-FORMATION IN DOUBLE CYTOKINE-DEFICIENT MICE REVEALS A CENTRAL ROLE FOR IL-10 IN POLARIZING BOTH T-HELPER CELL 1-TYPE AND T-HELPER CELL 2-TYPE CYTOKINE RESPONSES IN-VIVO

In response to i.v.-injected eggs of Schistosoma mansoni, normal mice develop a dominant type 2 response, whereas IL-10-deficient animals ge nerate a mixed type 1/type 2 cytokine profile and show reduced pulmona ry granuloma formation. IL-4-deficient mice, while displaying diminish ed type 2 responses and granulomatous inflammation, also do not fully default to a type 1 cytokine profile. Strikingly, mice doubly deficien t in IL-4 and IL-10 are completely defective in pulmonary granuloma fo rmation and develop a highly polarized type 1 cytokine pattern. In ana logous fashion, mice deficient in both IL-12 and IL-10 generate highly exacerbated type 2 cytokine responses, whereas in wild-type animals, IL-12 depletion minimally effects egg-induced cytokine production. Tog ether, these results argue first that IL-10 is an important endogenous down-regulator of type 2 as well as type 1 cytokine synthesis, and se cond, that its induction is critical for type 2 response polarization in vivo.