IN-VIVO EFFECTS OF INTERLEUKIN-10 ON CONTACT HYPERSENSITIVITY AND DELAYED-TYPE HYPERSENSITIVITY REACTIONS

Interleukin (IL) 10 is a recently discovered cytokine, originally isol ated from T-helper 2 (Th2) cells, which inhibits cytokine production o f T-helper 1 (Th1) cells. Because Th1 cells appear to be of importance during the contact hypersensitivity reaction (CHS) we hypothesized th at IL-10 might modulate the outcome of CHS in vivo. Intraperitoneal in jection of murine recombinant IL-10 (1000 ng) into naive mice 24, 72, or 120 h before sensitization by epicutaneous application of 2,4-dinit rofluorobenzene (DNFB) did not affect ear swelling when ears were chal lenged 5 d later. However, intraperitoneal injection of IL-10 into alr eady sensitized mice 24 h before challenge resulted in a significant s uppression of the ear swelling response, suggesting that under the con ditions employed IL-10 is able to block the effector phase, but not th e induction phase of CHS in vivo The suppression could be reversed by the concurrent injection of an IL-10 antibody. Moreover, heat inactiva tion of native IL-10 resulted in loss of the inhibitory capacity. When mice were sensitized by subcutaneous injection of trinitrophenyl-coup led spleen cells (DTH) instead of epicutaneous application of the hapt en (CHS), intraperitoneally-injected IL-10 suppressed the effector pha se, but also the induction phase of DTH. IL-10 did not inhibit the tox ic ear-swelling response induced by topical application of two irritan ts tested (croton oil or benzalkonium chloride). The capacity of IL-10 to suppress the effector phase of CHS and DTH supports an important r ole for this cytokine in the downregulation of type IV immune reaction s in vivo. The finding that IL-10 suppresses the induction of DTH, but not of CHS, further suggests that CHS and DTH are related but distinc t immune reactions.