S63
Workshops
Wl. Cytokines and therapy
IWi-1 Cytokines and therapy of immune-mediated
and autoimmune dermatoses
Martin RScken, Tilo Biedermann. Department of Dermatology,
Ludwig-Maximilians-University Munich, Germany
Delayed type hypersensitivity reactions (DTHR) normally pro-
tect against infectious diseases. Whoever when directed against
autoantigens they may induce organ specific auto-immune dis-
eases such as multiple sclerosis, autoimmune arthritis, diabetes
or psoriasis and, when directed to haptens on the skin, contact
hypersensitivity (CHS). These diseases affect more than 10%
of the population in industrialized countries. In mice, DTHR
may frequently be prevented by deviation of interferon g (IPN-
g) producing T cells (Thl) to interleukin 4 (IL-4) producing T
cells (Th2) during the initial activation of the T cells. However,
memory Thl responses are considered to be stable and can only
be controlled by conventional immunosuppression.
In vitro evidence showing that the lymphokine phenotype
of immune responses may retain some plasticity led us to
investigate therapeutic immune deviation of already established
DTHR in viva, using CHS as a model. During DTHR, such
as CHS, proinflammatory Thl cytokines dominate the early
phases of the reactions and Th2 cytokines the late phases. This
observation suggests that Thl initiate and that Th2 terminate
DTHR. So far it was only possible to aggravate or suppress the
effector phase of DTHR by IL-12 or anti-IL-4 and ameliorate
DTHR by IL-4. We now show that established DTHR can
not only be suppressed by IL-4 but also be efficiently treated
with hapten and IL-4. This therapeutic immune deviation with
IL-4 and hapten of firmly established CHS induced a novel
state of reactivity. Subsequent hapten exposures resulted in
an unusually early IL-4 expression, 4-6 hours after hapten
reexposure. Neutrophil recruitment, tissue swelling and tissue
destruction were strongly reduced, despite unchanged expres-
sion of Thl cytokines. The therapy was ineffective in IL-4.ko
mice. Thus, the dynamics of IL-4 expression are sensitive to
therapeutic strategies and may ultimately determine the course
of DTHR.
0WI-2 Cytokines and therapy of lymphoma
K. Thestrup-Pedersen. Department of Dermatology,
Marselisborg Hospital, University of Aarhus, DK-8000 Aarhus
C., Denmark
Lymphoma - including cutaneous T cell lymphoma - can be
treated with interferon. Most experience is with alpha-inter-
feron, where the success rate is over 50%. Advanced cases are
difficult to treat, but early cases of CTCL can show a very good
response to interferon theraph.
Side effects are flu-like symptoms, depression, and leu-
copenia. They are dose-related. One should also consider the
development of neutralizing antibodies towards interferon, if
therapy fails.
Interferon in combination with PUVA seems to have a syner-
gistic effect
I WI -3 Cytokines and psoriasis
M. Deleuran. Dept. of Dermatology, Aarhus University
Hospital, Aarhus, Denmark
Psoriasis is a common skin disease affecting approximately 2%
of the population. Expression of many different cytokines has
been demonstrated in psoriatic skin and the balance between
them is believed to be of major importance in the development
of the disease. A predominant expression of T”l pro-inilamma-
tory cytokines like IL-2 and IPNy and a low expression of Tt.t2
cytokines like IL-4 and IL-10 characterize psoriasis. Because
THY cytokines tend to inhibit THY activity there is reason to
believe that a shift to T”2 would be beneficial in psoriasis.
Very few data has been published concerning treatment of
psoriasis with cytokines. Recently, it has been shown that IL-10
may be of benefit in the treatment of psoriasis. We injected IL-4
intralesionally for 7 days in a double blind placebo controlled
study. IL-4 had neither great clinical effect nor serious side
effects in psoriasis. The data and the results of this study will
be presented in details.
WI-4 Cytokines and therapy of malignant
melanoma
S. Beissert. Dept. of Dermatology, Univ. of Miinster; Miinster;
Germany
The increasing incidence and improvable treatment modalities
of malignant melanoma underline the necessity to develop new
therapeutic regimens. Research in immunology and celI biol-
ogy has enhanced our knowledge of cytokines. Among these
cytokines, IL-2 and IFNol have been shown to be of therapeu-
tic benefit by possibly inducing antitumoral immune responses.
Clinical trials have indicated that cytokine monotherapies do not
improve response rates in stage IV disease. Yet, in an adjuvant
setting, high dose IFNu therapy has been shown to signifi-
cantly prolong survival rates. Combinations of predominantly
darcarbazine (DTIC) and II?& are used in adjuvant treatment
strategies of stage III disease and palliaqve,treatment of stage
IV disease. Additionally applied IL-2 in this regimen did not
further improve response rates. Other combination chemother-