Cytokines: Interleukins
149
Tab. 6
Disease correlates and possible scope for therapeutic/clinical intervention using interleukin
inhibitors.
Interleukin
Disease correlates
Possibilities for therapeutic/
clinical intervention
IL-1
– Gram-negative septacemia,
IL-1ra, soluble IL-1R (other
anti-endotoxic shock, hypotension
inflammatory agents, e.g. anti-TNF
α
)
– Rheumatoid arthritis
As above
–M
u
l
t
i
p
l
es
c
l
e
r
o
s
i
s
,
,
– Kawasaki syndrome (inflammation of
veins)
,,
– Myeloid leukemia
,,
– Insulin-dependent diabetes mellitus
(IDDM)
,,
IL-2
– Lymphoid leukemia
Soluble IL-2R (also anti-TNF
α
antibody)
– Systemic lupus erythematosus (SLE)
,,
– Graft-versus-host disease
,,
IL-3
– Cerebral malaria
Anti-IL-3, anti-GM-CSF, anti-IFN
γ
IL-4
– Allergy/asthma
Anti-IL-4, soluble IL-4R
– IDDM
,,
– Blepharitis (inflammatory eye lesion)
,,
IL-5
– Allergy/asthma
Anti-IL-5
– Eosinophilia
,,
IL-6
– Gram-negative septicemia
IL-1ra, soluble IL-1R, anti-TNF
α
– Multiple myeloma
Anti-IL-6, soluble IL-6R
IL-7
– Lymphoid leukemia
Anti-IL-7, soluble IL2R
IL-8
– Psoriasis
Signal transduction inhibitors
– Erythroderma
,,
IL-10
– Burkitt’s lymphoma
Anti-IL-10
– Malignant B-cell lymphomas in AIDS
patients
,,
IL-11
– Megakaryocytic leukemia
Anti-IL-11
IL-12
– Multiple sclerosis
Anti-IL-12
– Autoimmune diseases
,,
IL-20
– Psoriasis
Anti-IL-20
activated and expanded
ex vivo
,andthen
reinfused back into the patient with the
expectation that the TIL would home back
into tumors has shown some promise, but
again is complicated by side effects and
less-than-durable responses. Novel gene
therapy strategies involving the transduc-
tion of patients’ lymphocytes or Fbroblasts
with the IL-2 gene leading to constitutive
IL-2 production are now being tested.
So far, other interleukins despite their
proven
immunoregulatory
activities
in
vitro
,
have
not
yet
found
much
favor
among clinicians for the
treatment of
human diseases. IL-1, for example, has
been
shown
to
enhance
cellular
pro-
liferation
and
immune
responses,
but
given in high-dose schedules it is prob-
ably too profoundly toxic for safe use.
Similarly,
IL-4
can
act
as
a
stimula-
tor of lymphocytes, but its augmentation
of
IgE
secretion
and
thus
the
poten-
tial for inducing allergic responses may
disqualify it from being used clinically.
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