Schwarz A, Grabbe S, Riemann H, Aragane Y, Simon M, Manon S, Andrade S, Luger T A, Zlotnik A, Schwarz T
Department of Dermatology, University Münster, Germany.
J Invest Dermatol. 1994 Aug;103(2):211-6. doi: 10.1111/1523-1747.ep12393073.
Interleukin (IL) 10 is a recently discovered cytokine, originally isolated from T-helper 2 (Th2) cells, which inhibits cytokine production of T-helper 1 (Th1) cells. Because Th1 cells appear to be of importance during the contact hypersensitivity reaction (CHS) we hypothesized that IL-10 might modulate the outcome of CHS in vivo. Intraperitoneal injection of murine recombinant IL-10 (1000 ng) into naive mice 24, 72, or 120 h before sensitization by epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) did not affect ear swelling when ears were challenged 5 d later. However, intraperitoneal injection of IL-10 into already sensitized mice 24 h before challenge resulted in a significant suppression of the ear swelling response, suggesting that under the conditions employed IL-10 is able to block the effector phase, but not the induction phase of CHS in vivo. The suppression could be reversed by the concurrent injection of an IL-10 antibody. Moreover, heat inactivation of native IL-10 resulted in loss of the inhibitory capacity. When mice were sensitized by subcutaneous injection of trinitrophenyl-coupled spleen cells (DTH) instead of epicutaneous application of the hapten (CHS), intraperitoneally-injected IL-10 suppressed the effector phase, but also the induction phase of DTH. IL-10 did not inhibit the toxic ear-swelling response induced by topical application of two irritants tested (croton oil or benzalkonium chloride). The capacity of IL-10 to suppress the effector phase of CHS and DTH supports an important role for this cytokine in the downregulation of type IV immune reactions 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 distinct immune reactions.
白细胞介素（IL）-10是一种最近发现的细胞因子，最初从辅助性T细胞2（Th2）中分离出来，它可抑制辅助性T细胞1（Th1）的细胞因子产生。由于Th1细胞在接触性超敏反应（CHS）中似乎很重要，我们推测IL-10可能在体内调节CHS的结果。在通过经皮应用2,4-二硝基氟苯（DNFB）致敏前24、72或120小时，向未致敏小鼠腹腔注射鼠重组IL-10（1000 ng），5天后对耳部进行激发时，耳部肿胀未受影响。然而，在激发前24小时向已经致敏的小鼠腹腔注射IL-10，导致耳部肿胀反应显著受到抑制，这表明在所采用的条件下，IL-10能够在体内阻断CHS的效应阶段，但不能阻断其诱导阶段。同时注射IL-10抗体可逆转这种抑制作用。此外，天然IL-10的热灭活导致抑制能力丧失。当小鼠通过皮下注射三硝基苯基偶联的脾细胞进行致敏（迟发型超敏反应，DTH）而不是经皮应用半抗原（CHS）时，腹腔注射的IL-10不仅抑制了DTH的效应阶段，还抑制了其诱导阶段。IL-10不抑制经局部应用两种受试刺激物（巴豆油或苯扎氯铵）诱导的毒性耳部肿胀反应。IL-10抑制CHS和DTH效应阶段的能力支持了这种细胞因子在体内下调IV型免疫反应中的重要作用。IL-10抑制DTH诱导但不抑制CHS诱导这一发现进一步表明，CHS和DTH是相关但不同的免疫反应。
