Biomedical Engineering Reference
In-Depth Information
Table 8.10
Some pathogens (bacterial, fungal and protozoal) whose
phagocytic-mediated destruction is impaired in persons suffering from CGD.
Administration of IFN-
γ
, in most cases, enhances the phagocyte's ability to
destroy these pathogens. These agents can cause hepatic and pulmonary
infections, as well as genitourinary tract, joint and other infections
Staphylococcus aureus
Plasmodium fl aciparum
Listeria monocytogenes
Leishmania donovani
Chlamydia psittaci
Toxoplasma gondii
Aspergillus fumigatus
8.3.3 Medical applications of interferon-
γ
The most notable medical application of IFN-
relates to the treatment of CGD, a rare genetic
condition with a population incidence of between 1 in 250 00 and 1 in 1 000 000. Phagocytic
cells of patients suffering from CGD are poorly capable/incapable of ingesting or destroying
infectious agents such as bacteria or protozoa. As a result, patients suffer from repeated infec-
tions (Table 8.10), many of which can be life threatening.
Phagocytes from healthy individuals are normally capable of producing highly reactive oxida-
tive substances, such as hydrogen peroxide and hypochlorous acid, which are lethal to pathogens.
Production of these oxidative species occurs largely via a multicomponent NADPH oxidase sys-
tem (Figure 8.8). CGD is caused by a genetic defect in any component of this oxidase system that
compromises its effective functioning.
In addition to recurrent infection, CGD sufferers also exhibit abnormal infl ammatory responses
which include granuloma formation at various sites of the body (granuloma refers to a tissue out-
growth that is composed largely of blood vessels and connective tissue). This can lead to obstruc-
tion of various ducts, e.g. in the urinary and digestive tracts.
Traditionally, treatment of CGD entailed prophylactic administration of antimicrobial agents in
an attempt to prevent occurrence of severe infection. However, affected individuals still experi-
ence life-threatening infections, requiring hospitalization and intensive medical care, as often as
once a year. Attempts to control these infections rely on strong antimicrobial agents and leukocyte
transfusions.
Long-term administration of IFN-
γ
to CGD patients has proven effective in treating/moderat-
ing the symptoms of this disease. The recombinant human IFN-
γ
γ
used therapeutically is produced
in
E. coli
, and is termed IFN-
,
although it lacks the carbohydrate component. The product, usually sold in liquid form, is manufac-
tured by Genentech, who market it under the tradename Actimmune. The product is administered
on an ongoing basis, usually by s.c. injection three times weekly. In clinical trials, its administra-
tion, when compared with a control group receiving a placebo, resulted in a reduction in the:
γ
1b. It displays identical biological activity to native human IFN-
γ
•
incidence of life-threatening infections by 50 per cent or more;
•
incidence of total infections by 50 per cent or more;
•
number of days of hospitalization by threefold (and even when hospitalization was required, the
average stay was cut in half).
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