engleski

Interleukin-1ß but not several other cytokines abrogates tolerance to contact allergen

Background and purpose: The role of cytokines in co-stimulation and tolerance to antigens in cell-mediated immunity is not very well known. Here we studied the role of several interleukins, TNF-alpha and interferon-gamma on induction of tolerance to contact hypersensitivity to DNFB. Materials and Methods. CBA mice were given an i.v. injection of DNFB, and sensitized 7 days latter by skin painting with hapten. When ear-challenged 4 days letter, these mice became fully tolerant, as measured by ear swelling. The cytokines were given intraperitoneally within half an hour after i.v. injection of hapten. The concentration of IL-1 was determined by bioassay with D10s cells. Results. The reactivity to hapten could be significantly increased and the tolerance consequently abrogated, if 50 -1000 U of recombinant mouse IL-ß (rmIL-ß) was given to mice after injection of tolerogen. The tolerance could also be abrogated by LPS but not by the administration of some other cytokines (IL-1alpha, IL-2, IL-6, IFN-gamma and TNF-alpha). The concentration of IL-1 in serum after challenge with DNFB was increased in immunized mice, whereas its concentration in tolerant mice was significantly lower and not different from that in control, unsensitized mice. Similarly, spleen cells from immunized mice, when challenged in vitro with mitomycin C-treated DNFB-modified syngeneic spleen cells, secreted significant amounts of IL-1, while cells from tolerant mice secreted low amounts of IL-1, which were similar to secretion of unimmunized spleen cells. Under the same condition secretion of IL-4 and IL-10 was not statistically different between spleen cells from tolerant, immune or normal mice. Conclusions. These data suggest that the lack of IL-1 production by antigen-presenting cells may have been the cause of tolerance in this model and that suppressive mechanisms play minor if any role in this process.

contact hypersensitivity; tolerance; cytokines; interleukin-1ß

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