Biomedical Engineering Reference
In-Depth Information
9.3.2 Interleukin-1 biotechnology
IL-1 continues to be a focus of clinical investigation. This stems from its observed:
•
immunostimulatory effects;
•
ability to protect/restore the haematopoietic process during, or subsequent to, chemotherapy or
radiation therapy;
•
anti-proliferative effects against various human tumour cell lines grown
in vitro
, or in animal
models.
Most of these effects are most likely mediated not only directly by IL-1, but also by various ad-
ditional cytokines (including IL-2) induced by IL-1 administration.
The observed effects prompted initiation of clinical trials assessing IL-1's effi cacy in treating:
•
bone marrow suppression induced by chemo/radiotherapy;
•
various cancers.
) proved disappoint-
ing. No signifi cant anti-tumour response was observed in many cases, although side effects were
commonly observed. Virtually all patients suffered from fevers, chills and other fl u-like symptoms.
More serious side effects, including capillary leakage syndrome and hypotension, were also ob-
served and were dose limiting.
IL-1 thus displays toxic effects comparable to administration of TNF (see later), or high levels
of IL-2. However, several clinical studies are still underway, and this cytokine may yet prove
therapeutically useful, either on its own or, more likely, when administered at lower doses with
additional therapeutic agents.
Because of its role in mediating acute/chronic infl ammation, (downward) modulation of IL-1
levels may prove effective in ameliorating the clinical severity of these conditions. Again, several
approaches may prove useful in this regard, including administration of:
The initial fi ndings of some such trials (involving both IL-1
α
and IL-1
β
•
anti-IL-1 antibodies;
•
soluble forms of the IL-1 receptor;
•
the native IL-1 receptor antagonist.
Kineret is the tradename given to a recently approved product based on the latter strategy. In-
dicated in the treatment of rheumatoid arthritis, the product consists of a recombinant form of the
human IL-1 receptor antagonist. The 17.3 kDa, 153 amino acid product is produced in engineered
E. coli
and differs from the native human molecule in that it is non-glycosylated and contains an
additional N-terminal methionine residue (a consequence of its prokaryotic expression system).
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