TY - JOUR
T1 - Immunologic aspects of atopic dermatitis
AU - Hanifin, J. M.
N1 - Funding Information:
D irect autoradiographic identification of the epidermal The optim:tl penetration of [3HldThd, with respect to the growth fraction (GF) requires the delivery of tritiated thyconcentration of Azone over a range of0-4%, was achieved midine WHJdThd) to the skin during the time interval of at 2%. During the initial 24 h following a single topical an entire cell cycle. The GF in normal human epidermis application of j3H]dThd to hairless mice the labeling inhas not been directly measured using this technique because creased linearly with time. In vivo studie in hairless mice the systemic infusion of radioactive j3H jdT hd in benign produced a GF of 95% by both continuous systemic skin conditions is precluded by ethic:tl considerations. Studies [31-lldT hd infusion, and by twice daily topical [31-JjdThd. were undertaken to assess the feasibility of measuring the Azone vehicles induced epidermal hyperplasi3 which was epidermal GF in vivo by the topical delivery ofi3H]dThd. minimized by lowering the Azone concentration and by The percutaneous penetration of f3HldThd in various decreasing the frequency of 3pplications from 24 to 48 h. vehicles was evaluated to select an effective topical delivery These studies establish the rationale for using topical desystem. A vehicle consisting of Azone, isopropanol, and livery of [3H]dThd for the in vivo measurement of epiwater (2:49:49) was the best of4 different vehicles tested. dermal GF. J l11vest Denllalol 86:406-409, 1986 -- --- - - - - - - - - - - - - - - - - - - - - - - - - - - --- --- - - T he growth fraction (GF) is an important kinetic pa-rameter in experimentally defining the rate of epi-dcrnlJ! cell reproduction. T he GF of :t cell population is by definition that fraction of cells actually in the process of proliferation Jll. The traditi01nl method for measuring GFs requires a continuous systemic infusion of triti~ted thymidine WHidThd) and sequential biopsies for autoradiographic ana lysis to detect cell s synthesizing ON A during the J·'H ldThd infusion. When the percentage of labeled basal cells attains a plateau, essentially all actively proliferating cells have been labeled. The height of this plateau, expressed as the percentage of labeled cells. is an estimate of the GF for the cell population under investigation. Systemic infusion of J3HidThd has been used to measure GF in animals J21 and terminal cancer p::Hients J31. However ethical considerations preclude systemic 131-1 ldThd infusion in humans with benign skin conditions. Local intradermal injection of [31-lldThd given sequentially over the entire cell cycle greatly reduces the dosa ge of radioactive labeled drug needed to measure cell cycle time (Tc). The bricfTc in a psoriatic plaque (36 h) [4j permits the usc of multiple intradermal 1.11-1 ldThd injections in Manuscript rec~ived April I, l'iHS; accepted for publication October 21, I'Jtl5. Support~d in part by United Stat~s Public Health Service Grant AM 27110 from the National Institutes of Health and by the Southern California Dermatology Foundation. *This work was presented in part at rhe Ann ual Meetin g of the Western Regiona l Section of The Society for In vesti gative Dermatology, Ca rmel, California. February <J. I 'J83. Reprint reques ts ro: jerr y L. McC ull ough, Ph. D. , Department of Dermatology, California College of Mcdi inc, University of California, lrvinl·. Irvine. California 92717. Abbreviations: GF: growth fraction Ll: labclint,; indc-x SA: specific activity ]·11-ljdThd: tritiated thymidine Tc: cell cycle time measuring the GF [21. However, in healthy human skin therepeated trauma of multiple injections into the sa me site during the normal 13-day cell cycle would more than likely produce a proliferative ''wounding" response. and therefore an inaccurate measuremellt of GF. Topica l delivery of J3H ldThd sho uld minimize the systemic exposure of this radioactive compound and also avoid the trauma of repeated injections. The present study was therefore undertaken to assess the feasibility of using topical de livery o fJ-'1-1 JdThd as an altern ative in vivo method for measuring epiderma l G F. Our experiments were designed so as: (1) to sel ect an effective vehi ck for the topica l delivery of [-'H)dThd using an in vitro percutaneou · diffusion model; and (2) to investigate the time course of autoradiographic labeling in hairless mouse epidermis in vivo.
PY - 1990
Y1 - 1990
N2 - The immunology of atopic dermatitis is complex, multilayered, and multifaceted. In one realm are the IgE-mediated, type I hypersensitivity reactions that can be elicited in at least 80% of patients. A second realm is that associated with cell-mediated immunity and delayed-type hypersensitivity (type IV) reactions. Scattered between these immunologic paradigms are the various splinters: immune complex abnormalities, putative late-phase reactions, and cutaneous basophil hypersensitivity. The inflammatory lesion of atopic dermatitis probably is a composite of the many model reactions that investigators have glimpsed but never resolved into a reasonable concept.
AB - The immunology of atopic dermatitis is complex, multilayered, and multifaceted. In one realm are the IgE-mediated, type I hypersensitivity reactions that can be elicited in at least 80% of patients. A second realm is that associated with cell-mediated immunity and delayed-type hypersensitivity (type IV) reactions. Scattered between these immunologic paradigms are the various splinters: immune complex abnormalities, putative late-phase reactions, and cutaneous basophil hypersensitivity. The inflammatory lesion of atopic dermatitis probably is a composite of the many model reactions that investigators have glimpsed but never resolved into a reasonable concept.
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U2 - 10.1016/s0733-8635(18)30461-3
DO - 10.1016/s0733-8635(18)30461-3
M3 - Short survey
C2 - 2249365
AN - SCOPUS:0025011764
SN - 0733-8635
VL - 8
SP - 747
EP - 750
JO - Dermatologic Clinics
JF - Dermatologic Clinics
IS - 4