Regulation of the production of soluble IL-4 receptors in murine cutaneousleishmaniasis. The roles of IL-12 and IL-4

These studies were undertaken with the purpose of elucidating the key signa ls involved in the regulation of the production of soluble interleukin-9 re ceptors (sIL-4R) in mice during Th1 and Th2 responses to infection with the parasite Leishmania major, Our results showed that the production of sIL-4 R was consistently higher in lymph node cell cultures from animals mounting a predominant Th2 response (BALB/c mice), and that sIL-4R production paral leled that of IL-4 in both mouse strains, even in the presence of a dominan t Th1 response (C3H/FeJ mice), Consistently; administration of anti-IL-12 a ntibodies to infected C3H/FeJ mice induced a switch from a Th1- to a Th2-ty pe response and resulted in enhanced production of sIL-4R. Addition of rIL- 12 to, splenic cell cultures, however, was found not to have a direct effec t on sIL-4R production induced by IL-4 or T cell mitogens, Moreover, the pr oduction of sIL-4R appears to be little influenced by Th1-produced cytokine s, inasmuch as recombinant interferon-gamma or supernatants derived from an tigen-stimulated Th1 clones did not affect the production of sIL-4R by acti vated splenic cultures. Despite its correlation with Th2 responses, the pre sence of IL-4 was not an absolute requirement for the up-regulation of the expression of sIL-4R because increased levels could be induced on cells obt ained from IL-4(-/-) mice, These results indicate that, although enhanced s IL-4R production is a feature related to the activation and/or generation o f Th2 responses, it is not absolutely dependent on IL-4 or directly inhibit ed by IL-12 or Th1 cytokines.