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Summary Epidermal Langerhans' cell (LC) migration to the regional lymph node and beyond into central lymph was examined in sheep following topical application of the complete chemical carcinogen 7,12-dimethylbenz(a)anthracene(DMBA) or the contact sensitizing antigen 2,4,6-trinitrochlorobenzene (TNCB). This was facilitated by cannulating previously constructed pseudoafferent lymphatic vessels draining the skin treated with these agents or alternatively, the efferent lymphatic vessel of the regional lymph node.Application of DMBA resulted in a biphasic increase in LC migration. There was an initial increase in LC migration at 25 h with the maximum response (3.6 x 10^ LC/h) occurring approximately 5 days after DMBA treatment. In contrast, the contact sensitizing antigen TNCB caused enhanced LC migration within mitiutes of the application of antigen (3.3 x 10'' LC/h) and peak migration at 8-12 h.Examination of efferent lymph cells from the regional lymph node after DMBA treatment showed uncharacteristically large numbers of LC traversing the lymph node. These LC migration patterns suggest ditferent mechanisms may trigger the migration of LC from skin after the application of DMBA to those associated with the normal processes of antigen presentation.

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SUMMARYThe ability of the chemical carcinogen dimethylbenz(a)anthracene (DMBA) to deplete Langerhans' cells (LC) from murine skin is crucial to the development of antigen-specific suppression. This depletion is a consequence of the LC recognizing the DMBA as antigenic and migrating to the draining lymph nodes to attempt to elicit T-cell activation. This depletion also occurred following exposure to high doses of the contact sensitizers 2,4-dinitrofluorobenzene (DNFB), 2,4,6-trinitrochlorobenzene (TNCB) and fluorescein isothiocyanate (FITC). However, LC depletion was not significant at lower doses, even though these doses were sufficient to induce strong contact sensitivity responses. Application of the contact sensitizer, DNFB, through skin depleted of LC (by pretreatment with either the carcinogen DMBA or the antigen TNCB) failed to induce contact sensitivity. This immune nonresponsiveness was antigen specific, and could be transferred by spleen cells to naive mice, which were unable to respond to DNFB. Mouse skin treated with doses of TNCB, that did not cause LC depletion but still induced a normal contact hypersensitivity, retained its ability to initiate a normal immune response to DNFB. Together these findings demonstrate that carcinogens share some properties with antigens as they both cause LC depletion and interact with the immune system. Furthermore, it is this LC depletion, rather than carcinogen treatment, that is a critical factor which leaves the skin immunologically compromised and favours the induction of antigen-specific suppression.

Summary:We studied interleukin-6 (IL-6) levels on the day of transplantation in 31 patients undergoing autologous haemopoietic stem cell transplantation (SCT) (either peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation (BMT)) for neoplastic diseases to determine if there was a relationship between IL-6 level and rate of haemopoietic recovery, length of stay in hospital, and survival. There was no apparent delay in post-transplant recovery associated with elevated IL-6 levels. However, increased values of IL-6 tended to be associated with an increased length of stay in hospital (P = 0.083). There was a highly significant adverse association between higher IL-6 levels and survival following transplantation (P = 0.0001). This association remained significant (P = 0.013) in the uniform subgroup of patients with malignant lymphoma with chemosensitive disease who had undergone BMT (that is, excluding patients who had undergone PBSCT) (n = 13). Knowledge of IL-6 levels on the day of transplant has the potential to provide valuable prognostic information in patients undergoing autologous haemopoietic SCT. Bone Marrow Transplantation (2001) 28, 929-933.