In vivo effects of interleukin-10 on contact hypersensitivity and delayed-type hypersensitivity reactions.
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.
Department of Dermatology, University Münster, Germany.
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A
Schwarz
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Grabbe
H
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Riemann
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Y
Aragane
M
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Simon
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Manon
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Andrade
T A
TA
Luger
A
A
Zlotnik
T
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Schwarz
D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D003436:Croton Oil / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000209:etiology; D015536:Down-Regulation / Q000502:physiology; D006241:Haptens / Q000008:administration & dosage; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D016753:Interleukin-10 / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H
D001548:Benzalkonium Compounds; D006241:Haptens; D016753:Interleukin-10; D003436:Croton Oil